beta-carotene and Prostatic-Neoplasms

Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coffee; Diet; Dietary Supplements; gamma-Tocopherol; Humans; Lycopene; Male; Polyphenols; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selenium; Tea; United States

Vitamin supplementation is used for many purposes with mainly alleged benefits. One of these is the use of various vitamins for the prevention of prostate cancer.. We conducted a systematic review and meta-analysis on this topic. Pubmed, Embase and the Cochrane Database were searched; as well, we hand searched the references in key articles. Randomized controlled trials (RCTs), cohort studies and case-control studies were included. The review assessed the effect of supplemental vitamins on the risk of prostate cancer and on disease severity and death in men with prostate cancer.. Fourteen articles were included in the final assessment. Individually, a few of these studies showed a relationship between the ingestion of supplemental vitamins or minerals and the incidence or severity of prostate cancer, especially in smokers. However, neither the use of multivitamin supplementation nor the use of individual vitamin/mineral supplementation affected the overall occurrence of prostate cancer or the occurrence of advanced/metastatic prostate cancer or death from prostate cancer when the results of the studies were combined in a meta-analysis. We also conducted several sensitivity analyses by running meta-analysis using just the higher quality studies and just the RCTs. There were still no associations found.. There is no convincing evidence that the use of supplemental multivitamins or any specific vitamin affects the occurrence or severity of prostate cancer. There was high heterogeneity among the studies so it is possible that unidentified subgroups may benefit or be harmed by the use of vitamins.

Topics: Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Male; Minerals; Prostatic Neoplasms; Selenium; Vitamin E; Vitamins; Zinc

Several studies have evaluated the possible association between antioxidants vitamins or selenium supplement and the risk of prostate cancer, but the evidence is still inconsistent. We systematically searched PubMed, EMBASE, the Cochrane Library, Science Citation Index Expanded, Chinese biomedicine literature database, and bibliographies of retrieved articles up to January 2009. We included 9 randomized controlled trials with 165,056 participants; methodological quality of included trials was generally high. Meta-analysis showed that no significant effects of supplementation with beta-carotene (RR 0.97, 95% CI 0.90-1.05) (3 trials), vitamin C (RR 0.98, 95% CI 0.91-1.06) (2 trials), vitamin E (RR 0.96, 95% CI 0.85-1.08) (5 trials), and selenium (RR 0.78, 95% CI 0.41-1.48) (2 trials)versus placebo on prostate cancer incidence. The mortality of prostate cancer did not differ significantly by supplement of beta-carotene (RR 1.19, 95% CI 0.87 -1.65) (1 trial), vitamin C (RR 1.45, 95%CI 0.92-2.29) (1 trial), vitamin E (RR 0.85, 95%CI 0.58-1.24) (2 trials), and selenium (RR 2.98, 95% CI 0.12-73.16) (1 trial). Our findings indicate that antioxidant vitamins and selenium supplement did not reduce the incidence and mortality of prostate cancer, these data provide no support for the use of these supplements for the prevention of prostate cancer.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Male; Middle Aged; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Selenium; Vitamin E

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. The expert panel also concluded that it is unlikely that beta-carotene (whether from foods or supplements) has a substantial effect on the risk of this cancer. A recent review on environmental factors in human prostate cancer also found that there were protective effects of vitamin E, pulses, soy foods and high plasma 1,25-dihydroxyvitamin D levels. The Mediterranean diet is abundant in foods that may protect against prostate cancer and is associated with longevity and reduced cardiovascular and cancer mortality. Compared with many Western countries Greece has lower prostate cancer mortality and Greek migrant men in Australia have retained their low risk for prostate cancer. Consumption of a traditional Mediterranean diet, rich in bioactive nutrients, may confer protection to Greek migrant men, and this dietary pattern offers a palatable alternative for prevention of this disease.

Topics: beta Carotene; Calcium, Dietary; Carotenoids; Diet, Mediterranean; Dietary Fats; Humans; Incidence; Lycopene; Male; Prostatic Neoplasms; Selenium; Vegetables; Vitamin D

Epidemiological studies have shown marked variations in prostate cancer incidence and mortality across different geographic regions, leading to the rising interest in the role of nutrition in prostate cancer risk. There is also a large body of evidence that a diverse diet, rich in vegetables, can reduce the risk of prostate cancer. In this review, the role of various kinds of vegetables and their bioactive compounds associated with prostate cancer risk, and the underlying mechanisms of these associations are summarized. There is accumulating evidence to support the consumption of lycopene, in particular tomato and tomato-based products, as protective factors against prostate cancer. Evidence on the protective role of beta-carotene was inconsistent from cohort and case-control studies. Evidence on the effect of pulses or soy consumption on prostate cancer risk was limited but suggestive of decreased risk with increased pulses or soy consumption. However, the role of vitamin C, vitamin E, allium vegetables, and cruciferous vegetables on prostate cancer risk remains to be determined due to limited evidence. Although the impact on prostate cancer risk differs among various vegetables and their constituent nutrients, the overall benefits of plant based diet on cancer prevention and other diet-related diseases should be promoted.

Topics: Allium; Ascorbic Acid; beta Carotene; Brassicaceae; Carotenoids; Diet; Flavonoids; Humans; Lycopene; Male; Prostatic Neoplasms; Vegetables

Tomatoes are discussed to have an important role in the prevention of and therapy for prostate cancer (PCA). Whether or not they are also useful in the primary and secondary prevention of benign prostate hyperplasia (BPH) is not clear. This review summarises the results of original contributions with a focus on interventional studies. Whereas epidemiological studies on BPH prevention provide no evidence for a preventive potential of tomatoes and tomato products, the majority of interventional trials points to an increased DNA resistance against oxidative-induced damage. Even though their effect on a surrogate marker of the IGF pathway cannot be evaluated so far due to insufficient data, the consumption of tomatoes and tomato products may probably protect from PCA--at least when considering low-grade PCA. Thus, regular consumption of these foods can be recommended for the prevention of PCA. Tomato products might also be useful in the therapy for BPH and PCA. The intake of isolated lycopene does not protect from the development of PCA. However, in the doses achieved by consumption of tomato products, lycopene ingestion might also be effective in PCA therapy.

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Cohort Studies; DNA Damage; Evidence-Based Medicine; Humans; Lycopene; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Solanum lycopersicum; Time Factors

There are no established risk factors for prostate cancer other than age, ethnic group, and family history. For dietary factors, the WCRF/AICR reported that diets high in vegetables were possibly protective, and that regular consumption of red meat, fat, saturated/animal fat, and milk and any products possibly increased risk. Among nutritional factors, a protective effect of lycopene, vitamin E, selenium, and perhaps fish oil and phytoestrogens appear particularly promising, although no definite answers have yet emerged. Although hormonal influences are biologically plausible, observational studies of androgen have not produced consistent results. While, insulin-like growth factor 1 could be a risk factor. Based on these evidences, several chemoprevention trials were launched using 5-alpha reductase inhibitor, selenium, vitamin E and so on.

Topics: 5-alpha Reductase Inhibitors; beta Carotene; Dairy Products; Diet, Fat-Restricted; Diet, Vegetarian; Enzyme Inhibitors; Exercise; Finasteride; Fish Oils; Humans; Life Style; Male; Meat; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selenium; Vitamin E

Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges.

Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; beta Carotene; Breast Neoplasms; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Tamoxifen; Tretinoin; Urinary Bladder Neoplasms

Selenium and vitamin E are probably 2 of the most popular dietary supplements considered for use in the reduction of prostate cancer risk. This enthusiasm is reflected in the initiation of the Selenium and Vitamin E Chemoprevention Trial (SELECT). Is there sufficient evidence to support the use of these supplements in a large-scale prospective trial for patients who want to reduce the risk of prostate cancer? Results from numerous laboratory and observational studies support the use of these supplements, and data from recent prospective trials also add partial support. However, a closer analysis of the data reveals some interesting and unique associations. Selenium supplements provided a benefit only for those individuals who had lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, did not benefit and may have an increased risk for prostate cancer. The concept that supplements reduce prostate cancer risk only in those at a higher risk and/or those with lower plasma levels of these compounds is supported by trials examining beta-carotene supplements. Smokers may be the only individuals who benefit, as has also been shown with vitamin E supplementation. In 4 recent prospective studies, vitamin E was found to reduce the risk of prostate cancer in past/recent and current smokers and those with low levels of this vitamin. Vitamin E supplements in higher doses (> or =100 IU) were also associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers from a past prospective study. The dose of vitamin E in the SELECT trial (400 IU/day) is 8 times higher than what has been suggested to be effective (50 IU/day) by the largest randomized prospective trial in which the incidence rate of prostate cancer was used as an endpoint. Recent research also suggests that dietary vitamin E may be associated with a lower risk of prostate cancer than the vitamin E supplement. Additionally, recent results from all past cardiovascular prospective, randomized trials suggest that vitamin E shows little benefit for cardiovascular disease risk, especially at the dose being used in the SELECT trial. Other intriguing positive findings from past prospective studies of supplements suggest that aspirin and other nonsteroidal anti-inflammatory drugs have a role in reducing the risk of prostate cancer or other types of cancer (eg, colon cancer). It may be time to conduct a large costly trial to reconsider the use of selenium and vitamin E su

Topics: beta Carotene; Comorbidity; Dietary Supplements; Female; Humans; Male; Middle Aged; Prostatic Neoplasms; Selenium; Smoking; Vitamin E

CANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A, E, D and C. the results of these studies have been contradictory. Vitamin A and vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an activity similar to that of vitamin A. Beta-carotene was positively associated with risk of cancer of the prostate in one study while two others were unable to demonstrate any relationship. Lycopene, the red color in fruits and vegetables, particularly tomatoes, would contribute to a lower risk of prostate cancer.. Cadmium would increase the risk of cancer while selenium would have a protective effect. However studies concerning selenium carry certain methodological biases.

Topics: Aged; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cadmium; Carotenoids; Clinical Trials as Topic; Cohort Studies; Follow-Up Studies; Humans; Lycopene; Male; Mice; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selenium; Solanum lycopersicum; Time Factors; Trace Elements; Tumor Cells, Cultured; Vitamin A; Vitamin D; Vitamin E; Vitamins

Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging.

Topics: Age Factors; beta Carotene; Breast Neoplasms; Carotenoids; Colorectal Neoplasms; Dietary Fats; Dietary Fiber; Feeding Behavior; Humans; Incidence; Male; Neoplasms; Prostatic Neoplasms; Sex Factors

Retinol, the most biologically active form of vitamin A, might influence cancer-related biological pathways. However, results from observational studies of serum retinol and cancer risk have been mixed. We prospectively examined serum retinol and risk of overall and site-specific cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,104 men), conducted in 1985-1993, with follow-up through 2012. Serum retinol concentration was measured using reverse-phase high-performance liquid chromatography. Cox proportional hazards models estimated the association between baseline serum retinol quintile and overall and site-specific cancer risk in 10,789 cases. After multivariable adjustment, higher serum retinol was not associated with overall cancer risk (highest vs. lowest quintile: hazard ratio (HR) = 0.97, 95% confidence interval (CI): 0.91, 1.03; P for trend = 0.43). Higher retinol concentrations were, however, associated with increased risk of prostate cancer (highest vs. lowest quintile: HR = 1.28, 95% CI: 1.13, 1.45; P for trend < 0.0001) and lower risk of both liver and lung cancers (highest vs. lowest quintile: for liver, HR = 0.62, 95% CI: 0.42, 0.91; P for trend = 0.004; and for lung, HR = 0.80, 95% CI: 0.72, 0.88; P for trend < 0.0001). No associations with other cancers were observed. Understanding the mechanisms that underlie these associations might provide insight into the role of vitamin A in cancer etiology.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Body Weights and Measures; Cholesterol, HDL; Chromatography, High Pressure Liquid; Diet; Dietary Supplements; Double-Blind Method; Exercise; Finland; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Residence Characteristics; Smoking; Socioeconomic Factors

The aim of this study was to investigate the association between BMI (kg/m) and prostate cancer risk. BMI is a modifiable lifestyle factor and may provide a unique opportunity for primary prevention of prostate cancer if a causal association exists. Data from 11 886 men from the Carotene and Retinol Efficacy Trial (CARET, 1985-1996 with active follow-up through 2005) comprising current and former heavy smokers were analyzed. CARET was a multicenter randomized, double-blind placebo-controlled chemoprevention trial testing daily supplementation of 30 mg β-carotene+25 000 IU retinyl palmitate for primary prevention of lung cancer. Prostate cancer was a secondary outcome. Nonaggressive disease was defined as Gleason less than 7 and stage I/II. Aggressive disease was primarily defined as at least Gleason 7 or stage III/IV, and secondarily by excluding Gleason 3+4 from the first definition. BMI was calculated from measured weight and height. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer incidence between BMI categories. During follow-up, 883 men were diagnosed with prostate cancer. In the analysis of aggressive disease when Gleason 3+4 was excluded, men with a BMI of at least 35 kg/m had an increased rate of prostate cancer (HR: 1.80, 95% CI: 1.04-3.11, Ptrend=0.04) compared with men with BMI 18-24.9 kg/m. No other differences were seen in risk estimates for overall, nonaggressive or aggressive prostate cancer including all Gleason 7 cases, between BMI categories. Our results show an association between having a BMI of at least 35 kg/m and an increased risk of aggressive prostate cancer (not including Gleason 3+4 tumors), but do not support an association between BMI and risk of overall, aggressive disease including all Gleason 7, or nonaggressive prostate cancer within a population of current and former heavy smokers.

Topics: Aged; beta Carotene; Body Mass Index; Double-Blind Method; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Provitamins; Risk Factors; United States; Vitamin A; Vitamins

Impaired metabolism may play an important role in the pathogenesis of lethal prostate cancer, yet there is a paucity of evidence regarding the association. We conducted a large prospective serum metabolomic analysis of lethal prostate cancer in 523 cases and 523 matched controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (maximum 30 years). We identified 860 known biochemicals through an ultrahigh-performance LC-MS/MS platform. Conditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals of risk associated with 1-standard deviation (s.d.) increases in log-metabolite signals. We identified 34 metabolites associated with lethal prostate cancer with a false discovery rate (FDR) < 0.15. Notably, higher serum thioproline, and thioproline combined with two other cysteine-related amino acids and redox metabolites, cystine and cysteine, were associated with reduced risk (1-s.d. OR = 0.75 and 0.71, respectively; p ≤ 8.2 × 10

Topics: alpha-Tocopherol; Amino Acids; beta Carotene; Biomarkers, Tumor; Case-Control Studies; Chromatography, Liquid; Double-Blind Method; Fatty Acids; Humans; Logistic Models; Male; Metabolomics; Middle Aged; Odds Ratio; Prospective Studies; Prostatic Neoplasms; Risk Factors; Tandem Mass Spectrometry

The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases.. PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT.. With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group.. The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.

Topics: Aged; Antioxidants; beta Carotene; Bone Neoplasms; Cause of Death; Double-Blind Method; Humans; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Tolerance; Treatment Outcome

Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.. Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status.. Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9).. In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

Topics: Aged; alpha-Tocopherol; beta Carotene; Case-Control Studies; Genetic Association Studies; Humans; Hypothyroidism; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Thyroid Function Tests; Thyrotropin; Thyroxine

Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P(trend) = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Chromatography, High Pressure Liquid; Double-Blind Method; Female; Finland; Humans; Incidence; Male; Middle Aged; Placebos; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Registries; Risk Assessment; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A; White People

Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol and that statins may protect against aggressive disease. Confirmation in additional populations and examination of associations for lipoprotein subfractions are needed.. We examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort (n = 29,093). Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041), non-aggressive (n = 829), aggressive (n = 461), advanced (n = 412), and high-grade (n = 231) prostate cancer by categories of total and HDL cholesterol.. After excluding the first 10 years of follow-up, men with higher serum total cholesterol were at increased risk of overall (≥240 vs. <200 mg/dl: HR = 1.22, 95% CI 1.03-1.44, p-trend = 0.01) and advanced (≥240 vs. <200 mg/dl: HR = 1.85, 95% CI 1.13-3.03, p-trend = 0.05) prostate cancer. Higher HDL cholesterol was suggestively associated with a decreased risk of prostate cancer regardless of stage or grade.. In this population of smokers, high serum total cholesterol was associated with higher risk of advanced prostate cancer, and high HDL cholesterol suggestively reduced the risk of prostate cancer overall. These results support previous studies and, indirectly, support the hypothesis that statins may reduce the risk of advanced prostate cancer by lowering cholesterol.

Topics: Aged; alpha-Tocopherol; beta Carotene; Cholesterol; Cholesterol, HDL; Cohort Studies; Double-Blind Method; Finland; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Treatment Outcome

Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer. Prospective studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer. Similarly, serum β-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk. Using a prospective nested case-control study design, which minimized the possibility of disease effects on serum-vitamin concentrations, we report null associations for serum concentrations of folate, lycopene, β-carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.

Topics: Aged; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Folic Acid; Humans; Lycopene; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin E

Significant reductions in prostate cancer incidence and mortality were observed in men randomized to receive 50 mg supplemental vitamin E (alpha-tocopherol) per day in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We hypothesized that variation in key vitamin E transport genes might directly affect prostate cancer risk or modify the effects of vitamin E supplementation. Associations between prostate cancer risk and 13 polymorphisms in two genes, TTPA and SEC14L2, were examined in 982 incident prostate cancer cases and 851 controls drawn from the ATBC Study. There was no association between the genetic variants and prostate cancer risk. Significant interactions were observed, however, between two variants in SEC14L2 (IVS11+931A>G and IVS11-896A>T) and the trial alpha-tocopherol supplement such that vitamin E supplementation reduced prostate cancer risk among men who were homozygous for either common allele [odds ratios (OR) and 95% confidence intervals (95% CI), 0.52 (0.30-0.90) and 0.64 (0.46-0.88), respectively] and nonsignificantly increased risk among those who carried one or two copies of either variant allele [ORs and 95% CIs, 1.27 (0.90-1.79) and 1.21 (0.96-1.52), respectively; both P for interaction < 0.05]. Genotype-phenotype analyses revealed significant but modest differences in baseline circulating concentrations of alpha-tocopherol and serum responses to the vitamin E supplementation for several polymorphisms. This study shows that genetic variation in TTPA and SEC14L2 is associated with serum alpha-tocopherol but does not have a direct effect on prostate cancer. Our results do, however, suggest that polymorphisms in SEC14L2 may modify the effect of vitamin supplementation regimens on prostate cancer risk.

Topics: alpha-Tocopherol; beta Carotene; Carrier Proteins; Diet; Dietary Supplements; Double-Blind Method; Genetic Variation; Humans; Lipoproteins; Male; Meat; Middle Aged; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Regression Analysis; Risk Factors; Tissue Plasminogen Activator; Trans-Activators; Vitamin E

Previous studies suggest that carotenoids and tocopherols (vitamin E compounds) may be inversely associated with prostate cancer risk, yet little is known about how they affect prostate cancer progression and survival. We investigated whether serum alpha-tocopherol, beta-carotene, and retinol concentrations, or the alpha-tocopherol and beta-carotene trial supplementation, affected survival of men diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer Prevention Study, a randomized, double-blind, placebo-controlled primary prevention trial testing the effects of beta-carotene and alpha-tocopherol supplements on cancer incidence in adult male smokers in southwestern Finland (n = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method with deaths from other causes treated as censoring, and using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CI) adjusted for family history of prostate cancer, age at randomization, benign prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45-1.00), especially among cases who had received the alpha-tocopherol intervention of the trial and who were in the highest quintile of alpha-tocopherol at baseline (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26; 95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta-carotene had no apparent effects on survival. These findings suggest that higher alpha-tocopherol (and not beta-carotene or retinol) status increases overall prostate cancer survival. Further investigations, possibly including randomized studies, are needed to confirm this observation.

Topics: Aged; alpha-Tocopherol; beta Carotene; Dietary Supplements; Double-Blind Method; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Vitamin A

Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. We investigated whether serum alpha-tocopherol or intake of vitamin E (eight tocopherols and tocotrienols) was associated with prostate cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency questionnaire and food chemistry analyses. Proportional hazard models were used to determine multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). Higher serum alpha-tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest quintile; Ptrend = 0.03) and was strongly and inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; Ptrend = 0.002). The inverse serum alpha-tocopherol-prostate cancer association was greater among those who were supplemented with either alpha-tocopherol or beta-carotene during the trial. There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols. In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer.

Topics: Aged; Anticarcinogenic Agents; Antioxidants; beta Carotene; Chromatography, High Pressure Liquid; Cohort Studies; Diet; Dietary Supplements; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Smoking; Vitamin E

Topics: Age Factors; Aged; alpha-Tocopherol; beta Carotene; Case-Control Studies; Double-Blind Method; Finland; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin D; Vitamins

The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) may play a role in prostate carcinogenesis. We examined the association between the PPAR-gamma Pro12Ala polymorphism and prostate cancer risk in a cohort of Finnish male smokers. In a nested case-control analysis that included 193 prostate cancer cases and 188 matched controls, we found no significant association between this polymorphism and prostate cancer risk (odds ratio, OR=1.27, 95% confidence interval, CI: 0.83-1.94), or significant trend or association with tumor stage (OR=1.28, 95% CI: 0.54-3.04 for metastatic disease) or grade (OR=1.57, 95% CI: 0.63-3.91 for poorly differentiated disease). The Pro12Ala polymorphism does not appear to play a significant role in prostate cancer risk in this cohort of men.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; Amino Acid Substitution; Anticarcinogenic Agents; beta Carotene; Case-Control Studies; Cell Differentiation; Cohort Studies; DNA Mutational Analysis; Finland; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Receptors, Cytoplasmic and Nuclear; Risk; Smoking; Transcription Factors

beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers, Tumor; Carotenoids; Case-Control Studies; Double-Blind Method; Female; gamma-Tocopherol; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Statistics as Topic; Treatment Outcome; Vitamin A

We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Codon; DNA Repair; DNA-Binding Proteins; Eating; Follow-Up Studies; Gene Frequency; Genotype; Humans; Lycopene; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Polymorphism, Genetic; Prostatic Neoplasms; Risk Factors; Treatment Outcome; Vitamin E; X-ray Repair Cross Complementing Protein 1

The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics.. Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models.. 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8).. The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Colonic Neoplasms; Double-Blind Method; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States

The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene.. Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits.. Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged.. These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Case-Control Studies; Colonic Neoplasms; Dietary Supplements; Double-Blind Method; Epidemiologic Studies; Follow-Up Studies; Humans; Lung Neoplasms; Lymphoma; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Risk; Smoking

5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Anticarcinogenic Agents; Aspirin; beta Carotene; Boston; Double-Blind Method; Heart Diseases; Humans; Isoenzymes; Leucine; Male; Middle Aged; Neoplasms; Polymorphism, Genetic; Prostatic Neoplasms; Risk Factors; Valine; White People

Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers.. A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated.. We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death.. Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Topics: Anticarcinogenic Agents; beta Carotene; Double-Blind Method; Humans; Incidence; Male; Prostatic Neoplasms; Treatment Outcome; Vitamin E

The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07).

Topics: Aged; beta Carotene; Dietary Supplements; Double-Blind Method; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Selenium; Smoking; Vitamin E

Topics: Antioxidants; beta Carotene; Carotenoids; Coronary Disease; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Vitamin E

This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify potential effect modifiers.. Utilizing data from the Singapore Prostate Cancer Study, a hospital-based case-control study, we measured the serum concentrations of 15 different forms of vitamins A and E in 156 prostate cancer patients and 118 control subjects, using a high-performance liquid chromatography technique. These forms included retinol, lutein, zeaxanthin, α-cryptoxanthin, β-cryptoxanthin, α-carotene, β-carotene, lycopene, ubiquinone, δ-tocopherol, γ-tocopherol, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol. The odds ratio and 95% confidence interval for associations between vitamin A and E and prostate cancer risk were estimated using logistic regression models after adjustment for potential confounders. The analyses were further stratified by smoking and alcohol consumption status. The mixture effect of micronutrient groups was evaluated using weighted quantile sum regression.. Higher concentrations of retinol, lutein, α-carotene, β-carotene, ubiquinone, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol were significantly and positively associated with overall prostate cancer risk. Among ever-smokers, associations were stronger for lutein, β-cryptoxanthin and β-carotene compared with never-smokers. Among regular alcohol drinkers, associations were stronger for lutein, β-cryptoxanthin, ubiquinone, γ-tocotrienol and α-tocotrienol compared with non-regular alcohol drinkers. Retinol and α-tocotrienol contributed most to the group indices 'vitamin A and provitamin A carotenoids' and 'vitamin E', respectively.. Several serum vitamin A and E forms were associated with prostate cancer risk, with significant effect modification by smoking and alcohol consumption status. Our findings shed light on prostate cancer etiology.

Topics: alpha-Tocopherol; beta Carotene; Beta-Cryptoxanthin; Case-Control Studies; Humans; Lutein; Male; Prostatic Neoplasms; Singapore; Tocotrienols; Ubiquinone; Vitamin A

According to the International Agency for Research on Cancer, some hair dye chemicals are considered mutagenic and carcinogenic in humans. One hospital-based study reported a positive association between hair dye use and prostate cancer risk, but no prospective analyses have been conducted.. This study investigated the association between hair dye use and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort, a large, well-characterized cohort of 29,133 male Finnish smokers. Participants completed questionnaires regarding lifestyle, medical, and risk factor information, including the use of hair dye, which was available for 98.8% of the cohort (28,795 men). Prostate cancer cases were identified through linkage with the Finnish Cancer Registry and the Finnish Mortality Register. Hazard ratios (HRs) and confidence intervals (CIs) were estimated via multivariable Cox proportional hazards regression.. During a 28-year period of observation, 2703 incident prostate cancer cases were diagnosed. As reported at the baseline, 75 men used hair dye, and 13 of these men were subsequently diagnosed with prostate cancer. After adjustments for potential confounders, men who used hair dyes experienced substantially higher prostate cancer risk than men who did not (HR, 1.77; 95% CI, 1.03-3.05).. This first prospective investigation of hair dye use and prostate cancer suggests that personal hair dye use may be related to increased risk. The findings warrant re-examination in other prospective cohorts along with studies evaluating specific hair dyes and possible underlying biological mechanisms.

Topics: alpha-Tocopherol; beta Carotene; Cohort Studies; Hair Dyes; Humans; Male; Prostatic Neoplasms; Risk Factors

Epidemiologic studies suggest lycopene and tomato intake are inversely associated with human prostate cancer incidence. In the genetically driven murine prostate carcinogenesis model transgenic adenocarcinoma of the mouse prostate (TRAMP), prostate cancer is inhibited by feeding of lycopene or tomatoes, and these effects are modulated by the β-carotene oxygenase 2 (Bco2) genotype.. We sought insight into this interaction through evaluation of prostate gene expression patterns during early TRAMP carcinogenesis.. Three-week-old TRAMP/+ or TRAMP/- × Bco2+/+ or Bco2-/- mice were fed a control, lycopene beadlet, or 10% tomato powder-containing semipurified diet (providing 0, 384 and 462 mg lycopene/kg diet, respectively) for 5 wk. Gene expression patterns were evaluated by prostate cancer- and cholesterol and lipoprotein metabolism-focused arrays at age 8 wk.. The TRAMP genotype profoundly alters gene expression patterns, specifically inducing pathways associated with cell survival [z-score = 2.09, -log(P value) = 29.2, p53 signaling (z-score 1.13, -log(P value) = 13.5], and phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling [z-score = 0.302, -log(P value) = 12.1], while repressing phosphatase and tensin homolog (PTEN) signaling [(z-score = -0.905, -log(P value) = 12.3], cholesterol synthesis [z-score = -1.941, -log(P-value) = 26.2], and LXR/RXR pathway activation [z-score = -1.941, -log(P value) = 23.1]. In comparison, lycopene- and tomato-feeding modestly modulate strong procarcinogenic TRAMP signaling. Lycopene decreased gene expression related to carcinogenesis [ Nkx3-1(NK3 homeobox 1)], tomato feeding increased expression of a gene involved in circadian regulation [Arntl (aryl hydrocarbon receptor nuclear translocator like)], and tomato and/or lycopene increased expression of genes involved in lipid metabolism [Fasn (fatty acid synthase), Acaca(acetyl-CoA carboxylase alpha), Srebf1 (sterol regulatory element binding transcription factor 1), Hmgcr (3-hydroxy-3-methylglutaryl-coA reductase), and Ptgs1 (prostaglandin-endoperoxide synthase 1)] (all P < 0.05). The impact of Bco2 genotype was limited to a subset of lycopene-impacted genes [Apc (adenomatous polyposis coli), Mto1 (mitochondrial TRNA translation optimization 1), Nfkb1 (nuclear factor kappa B subunit 1), andRbm39 (RNA binding motif protein 39)].. The TRAMP genotype strongly impacts procarcinogenic gene expression prior to emergence of histopathologic disease. Dietary tomato and lycopene modestly temper these processes, while Bco2 genotype has a limited impact at this early stage. These observed patterns provide insight into the complex interactions between a dietary variable, here tomatoes and lycopene, genes impacting nutrient metabolism, and their modulating influences on oncogene-driven prostate carcinogenesis. These findings provide further mechanistic support, consistent with cancer outcomes in rodents experiments and human epidemiologic studies.

Topics: Animals; beta Carotene; Carcinogenesis; Carotenoids; Diet; Dioxygenases; Gene Expression; Genotype; Lycopene; Male; Mice; Oxygenases; Prostate; Prostatic Neoplasms; Solanum lycopersicum

Investigate the relationship between serum α-tocopherol concentration and long-term risk of prostate cancer, and evaluate the interaction with vitamin E-related genetic variants and their polygenic risk score (PRS).. We conducted a biochemical analysis of 29,102 male Finnish smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and 2724 prostate cancer cases were identified during 28 years of follow-up. Cox proportional hazards models examined whether serum α-tocopherol concentrations were associated with prostate cancer risk. Among 8383 participants, three SNPs related to vitamin E status (rs964184, rs2108622, and rs11057830) were examined to determine whether they modified the relationship between serum α-tocopherol concentrations and prostate cancer risk, both individually and as a PRS using logistic regression models.. No association was observed between serum α-tocopherol and prostate cancer risk (fifth quintile (Q5) vs. Q1 hazard ratio (HR) = 0.87, 95% confidence interval (95% CI) 0.75, 1.02; P-trend = 0.57). Though no interactions were seen by population characteristics, high α-tocopherol concentration was associated with reduced prostate cancer risk among the trial α-tocopherol supplementation group (Q5 quintile vs. Q1 HR = 0.79, 95% CI 0.64, 0.99). Finally, no associated interaction between the three SNPs or their PRS and prostate cancer risk was observed.. Although there was a weak inverse association between α-tocopherol concentration and prostate cancer risk over nearly three decades, our findings suggest that men receiving the trial α-tocopherol supplementation who had higher baseline serum α-tocopherol concentration experienced reduced prostate cancer risk. Vitamin E-related genotypes did not modify the serum α-tocopherol-prostate cancer risk association.

Topics: alpha-Tocopherol; beta Carotene; Humans; Male; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Risk Factors; Vitamin E

Human plasma and tissue lycopene concentrations are heterogeneous even when consuming controlled amounts of tomato or lycopene.. Our objective is to determine whether single nucleotide polymorphisms (SNPs) in or near known or putative carotenoid metabolism genes [β-carotene 15,15' monooxygenase 1 (BCO1), scavenger receptor class B type 1 (SCARB1), ATP-binding cassette transporter subfamily A member 1 (ABCA1), microsomal triglyceride transfer protein (MTTP), apolipoprotein B-48, elongation of very long chain fatty acids protein 2 (ELOVL2), and ATP-binding cassette subfamily B member 1 (ABCB1), and an intergenic superoxide dismutase 2, mitochondrial-associated SNP] are predictive of plasma lycopene responses to steady state tomato juice consumption.. Secondary linear regression analyses of data from a dose-escalation study of prostate cancer patients [n = 47; mean ± SEM age: 60 ± 1 y; BMI (in kg/m2): 32 ± 1] consuming 0, 1, or 2 cans of tomato-soy juice/d (163 mL/can; 20.6 mg lycopene 1.2 mg β-carotene/can) for 24 ± 0.7 d before prostatectomy were conducted to explore 11 SNP genotype effects on the change in plasma lycopene and plasma and prostate tissue concentrations of lycopene, β-carotene, phytoene, and phytofluene.. Two BCO1 SNP genotypes were significant predictors of the change in plasma lycopene, with SNP effects differing in magnitude and direction, depending on the level of juice intake (rs12934922 × diet group P = 0.02; rs6564851 × diet group P = 0.046). Further analyses suggested that plasma β-carotene changes were predicted by BCO1 rs12934922 (P < 0.01), prostate lycopene by trending interaction and main effects of BCO1 SNPs (rs12934922 × diet group P = 0.09; rs12934922 P = 0.02; rs6564851 P = 0.053), and prostate β-carotene by BCO1 SNP interaction and main effects (rs12934922 × diet group P = 0.01; rs12934922 P < 0.01; rs7501331 P = 0.02).. In conclusion, SNPs in BCO1 and other genes may modulate human plasma and prostate tissue responses to dietary lycopene intake and warrant validation in larger, human controlled feeding intervention and cohort studies. Genetic variants related to carotenoid metabolism may partially explain heterogeneous human blood and tissue responses and may be critical covariates for population studies and clinical trials. This trial was registered at clinicaltrials.gov as NCT01009736.

Topics: beta Carotene; beta-Carotene 15,15'-Monooxygenase; Beverages; Carotenoids; Genotype; Humans; Linkage Disequilibrium; Lycopene; Male; Middle Aged; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Solanum lycopersicum; Soybean Proteins

Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers.. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability.. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression.. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P < 0.001). Among men with Gleason score ≤ 3 + 4, higher lycopene levels were associated with lower FGA (P = 0.04).. Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of prostate cancer early in its natural history.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Cross-Sectional Studies; DNA Repair; Genomic Instability; Genotype; Humans; Lycopene; Male; Middle Aged; Neoplasm Grading; Odds Ratio; Polymorphism, Single Nucleotide; Prostate; Prostatectomy; Prostatic Neoplasms; Risk Factors; Superoxide Dismutase

Despite decades of concerted epidemiological research, relatively little is known about the etiology of prostate cancer. As genome-wide association studies have identified numerous genetic variants, so metabolomic profiling of blood and other tissues represents an agnostic, "broad-spectrum" approach for examining potential metabolic biomarkers of prostate cancer risk. To this end, we conducted a prospective analysis of prostate cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort based on 200 cases (100 aggressive) and 200 controls (age- and blood collection date-matched) with fasting serum collected up to 20 years prior to case diagnoses. Ultrahigh performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy identified 626 compounds detected in >95% of the men and the odds ratio per 1-standard deviation increase in log-metabolite levels and risk were estimated using conditional logistic regression. We observed strong inverse associations between energy and lipid metabolites and aggressive cancer (p = 0.018 and p = 0.041, respectively, for chemical class over-representation). Inositol-1-phosphate showed the strongest association (OR = 0.56, 95% CI = 0.39-0.81, p = 0.002) and glycerophospholipids and fatty acids were heavily represented; e.g., oleoyl-linoleoyl-glycerophosphoinositol (OR = 0.64, p = 0.004), 1-stearoylglycerophosphoglycerol (OR=0.65, p = 0.025), stearate (OR=0.65, p = 0.010) and docosadienoate (OR = 0.66, p = 0.014). Both alpha-ketoglutarate and citrate were associated with aggressive disease risk (OR = 0.69, 95% CI = 0.51-0.94, p = 0.02; OR = 0.69, 95% CI = 0.50-0.95, p = 0.02), as were elevated thyroxine and trimethylamine oxide (OR = 1.65, 95% CI = 1.08-2.54, p = 0.021; and OR = 1.36, 95% CI = 1.02-1.81, p = 0.039). Serum PSA adjustment did not alter the findings. Our data reveal several metabolomic leads that may have pathophysiological relevance to prostate carcinogenesis and should be examined through additional research.

Topics: Adenocarcinoma; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Humans; Male; Metabolome; Metabolomics; Middle Aged; Prospective Studies; Prostatic Neoplasms

Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90-0.99, Ptrend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81-0.99, Ptrend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71-0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99-1.15), Ptrend = 0.06. This association turned significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.

Topics: Adult; beta Carotene; Body Mass Index; Breast Neoplasms; Carotenoids; Case-Control Studies; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Cryptoxanthins; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Logistic Models; Lung Neoplasms; Lycopene; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Vitamin A

Solar ultraviolet radiation exposure has been inversely related to prostate cancer incidence and mortality, possibly mediated through vitamin D status. Pigmentation-related traits influence endogenous vitamin D synthesis and may alter risk of prostate cancer.. We examined prostate cancer in relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982 out of 20 863 men. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazards models.. Prostate cancer risk did not differ by eye colour or skin phototype. Men with naturally red hair were significantly less likely to develop prostate cancer (HR=0.46, 95% CI 0.24-0.89) than men with light brown hair (reference).. The red hair phenotype, which results from polymorphisms in the melanocortin-1-receptor (MC1R) gene, is associated with lower risk of prostate cancer. This pigmentation-related trait may influence prostate cancer development either directly, through genetic effects or regulatory mechanisms related to MC1R, another nearby gene, or other pigmentation genes, or indirectly, through associations with other exposures such as sunlight or vitamin D status.

Topics: Aged; alpha-Tocopherol; beta Carotene; Disease Susceptibility; Eye Color; Finland; Hair Color; Humans; Male; Middle Aged; Phenotype; Proportional Hazards Models; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Registries; Skin Pigmentation

Results from epidemiologic studies on the association between circulating carotenoid concentrations and the risk of prostate cancer are still inconsistent. We studied whether serum concentrations of carotenoids were associated with the risk of developing prostate cancer. The study population consisted of 997 middle-aged Finnish men (56.1 ± 6.6 yr) in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids were measured by high-performance liquid chromatography. Subjects were classified into tertiles according to their serum concentrations of antioxidants. Relative risks (RRs) were estimated by using the Cox proportional hazard models. During the mean follow-up time of 15 yr, a total of 68 prostate cancer cases occurred. After adjusting for age, examination yr, family history of cancer, BMI, pack-yr of smoking, alcohol consumption, education, physical activity, serum total cholesterol, and serum α-linolenic acid, men in the highest tertile of serum concentrations of β-carotene had 2.3-fold higher risk of prostate cancer as compared to those in the lowest tertile (RR = 2.29, 95% CI: 1.12-4.66; P = 0.023). α-Tocopherol and retinol were not associated with prostate cancer. This prospective study suggests that high-serum β-carotene concentrations may increase the risk of prostate cancer in middle-aged men.

Topics: Adult; Aged; Alcohol Drinking; alpha-Linolenic Acid; alpha-Tocopherol; Antioxidants; beta Carotene; Cholesterol; Chromatography, High Pressure Liquid; Finland; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Surveys and Questionnaires; Vitamin A

Oral administration of β-carotene (BC) was found to exert opposite effects on plasma levels of vascular endothelial growth factor (VEGF) in two animal models. One study in nude mice injected via tail vein with hepatocarcinoma SK-Hep-1 cells showed that BC decreases the plasma VEGF level, whereas the other study in nude mice injected subcutaneously with prostate tumor PC-3 cells showed that BC increases the plasma VEGF level. Herein we investigated whether BC (0.5-20 μM) possesses diverse effects on VEGF secretion in SK-Hep-1, PC-3 and melanoma B16F10 cells. We found that incubation of SK-Hep-1 cells with BC (1-20 μM) for 6 h significantly decreased VEGF secretion, whereas BC (1-10 μM) significantly increased the VEGF secretion in PC-3 cells. However, these effects disappeared at 12 h of incubation. Similar effects occurred in VEGF mRNA and protein expression after treatment of SK-Hep-1 and PC-3 cells with BC for 6 h. In contrast, BC (0.5-20 μM) did not affect mRNA and protein expression and secretion of VEGF in B16F10 cells. We also found that the proliferation of SK-Hep-1 and B16F10 cells was significantly inhibited by 20 μM BC at 6 and 12 h of incubation, whereas the proliferation of PC-3 cells was significantly inhibited by 20 μM BC at 12 h of incubation. In summary, the present study demonstrated the tumor-specific effect of BC on VEGF secretion in different cancer cell lines.

Topics: Animals; beta Carotene; Carcinoma, Hepatocellular; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Mice; Prostatic Neoplasms; RNA, Messenger; Vascular Endothelial Growth Factor A

In this study, we evaluated the efficacy of lycopene against the growth of prostate cancer in vivo.. Athymic nude mice were implanted subcutaneously with human androgen-independent prostate carcinoma PC-3 cells. They were supplemented with a low or a high dose of lycopene (4 and 16 mg/kg) and a single dose of β-carotene (16 mg/kg) twice a week for 7 wk. At the end of the experiment, both lycopene and β-carotene strongly inhibited the tumor growth, as evidenced by the decrease in tumor volume and tumor weight. High-dosage lycopene and β-carotene significantly decreased the expression of proliferating cell nuclear antigen in tumor tissues and increased the levels of insulin-like growth factor-binding protein-3 in plasma. In addition, high-dosage lycopene supplementation significantly decreased the vascular endothelial growth factor (VEGF) levels in plasma. In contrast, β-carotene supplementation significantly increased the VEGF levels, as compared with tumor control group.. Lycopene and β-carotene supplementation suppressed the growth of prostate tumor cells, and the effects are likely associated with reduction of proliferation (attenuation of proliferating cell nuclear antigen expression) and with interference of the insulin-like growth factor 1 signaling (increased plasma insulin-like growth factor-binding protein-3 levels). Furthermore, the inhibition of VEGF by lycopene suggests that the antitumor mechanisms of lycopene also involve anti-angiogenesis.

Topics: Androgens; Animals; Anticarcinogenic Agents; beta Carotene; Carcinoma; Carotenoids; Cell Line, Tumor; Dietary Supplements; Humans; Insulin-Like Growth Factor Binding Protein 3; Lycopene; Male; Mice; Mice, Nude; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Random Allocation; Time Factors; Tumor Burden; Vascular Endothelial Growth Factors; Xenograft Model Antitumor Assays

The aim of this study was to determine whether serum concentrations of micronutrients, antioxidants and vitamins predict rate of disease progression in untreated, localised prostate cancer. Patients with localised prostatic adenocarcinoma on a prospective study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies. Disease progression was defined as either adverse histology on repeat biopsy (primary Gleason grade >or=4 or >50% positive cores of total) or radical treatment for PSA velocity >1 ng ml(-1) year(-1). Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol, gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, retinol and selenium. One hundred four patients were evaluable, with a median follow-up of 2.5 years. Thirty-eight patients experienced disease progression, 13 biochemical and 25 histologic progression. Median time to disease progression was 2.62 years. No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol (p = 0.86), gamma-tocopherol (p = 0.84), alpha-carotenoid (p = 0.66), beta-carotene (p = 0.65), lycopene (p = 0.0.15), retinol (p = 0.76) or selenium (p = 0.76). No significant association was seen between serum levels of the micronutrients, antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity. Our data do not support the hypothesis that high serum concentrations of micronutrients, antioxidants and vitamins prevent disease progression in men with localised prostate cancer.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Humans; Lycopene; Male; Micronutrients; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Vitamin E

Many studies have evaluated the association between vitamin and mineral supplement use and the risk of prostate cancer, with inconclusive results.. The authors examined the relation of use of multivitamins as well as several single vitamin and mineral supplements to the risk of prostate cancer risk among 1,706 prostate cancer cases and 2,404 matched controls using data from the hospital-based case-control surveillance study conducted in the United States. Odds ratios (OR) and 95% confidence intervals (CI) for risk of prostate cancer were estimated using conditional logistic regression model.. For use of multivitamins that did not contain zinc, the multivariable odds ratios of prostate cancer were 0.6 for 1-4 years, 0.8 for 5-9 years, and 1.2 for 10 years or more, respectively (p for trend = 0.70). Men who used zinc for ten years or more, either in a multivitamin or as a supplement, had an approximately two-fold (OR = 1.9, 95% CI: 1.0, 3.6) increased risk of prostate cancer. Vitamin E, beta-carotene, folate, and selenium use were not significantly associated with increased risk of prostate cancer.. The finding that long-term zinc intake from multivitamins or single supplements was associated with a doubling in risk of prostate cancer adds to the growing evidence for an unfavorable effect of zinc on prostate cancer carcinogenesis.

Topics: Adult; Aged; beta Carotene; Case-Control Studies; Dietary Supplements; Folic Acid; Humans; Male; Middle Aged; Odds Ratio; Prostatic Neoplasms; Risk Factors; Vitamin E; Vitamins; Zinc

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures. We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); -2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3 [endothelial NOS; IVS1-762C>T, Ex7-43C>T (D258D), IVS7-26A>G, Ex8-63G>T (E298D) and IVS15-62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency matched to controls (n = 1842), by age, race, time since initial screening and year of blood draw. An antioxidant score [range 3-12; low (3-7) versus high (8-12)] was created by summing the quartile levels of vitamin E, beta-carotene and lycopene, which were coded from 1 to 4, respectively. The global tests for all eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A-2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P = 0.005), especially for aggressive cancer (stage III-IV or Gleason score > or = 7) (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate cancer risk (odds ratio = 1.24, 95% confidence interval = 1.00-1.54), whereas the IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66-0.90). The NOS3 IVS7-26GG was associated with increased prostate cancer risk (1.33, 1.07-1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18-2.19; P(interaction) = 0.01). Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Genotype; Humans; Lycopene; Male; Middle Aged; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Prostatic Neoplasms; Risk Factors; Vitamin E

The aim of this study was to evaluate the inhibitory growth effects of different potential chemopreventive agents in vitro and to determine their influence on PSA mRNA and protein expression with an established screening platform.. LNCaP and C4-2 cells were incubated with genistein, seleno-L-methionine, lycopene, DL-alpha-tocopherol, and trans-beta-carotene at three different concentrations and cell growth was determined by the MTT assay. PSA mRNA expression was assessed by quantitative real-time RT-PCR and secreted PSA protein levels were quantified by the microparticle enzyme immunoassay.. Genistein, seleno-l-methionine and lycopene inhibited LNCaP cell growth, and the proliferation of C4-2 cells was suppressed by seleno-L-methionine and lycopene. PSA mRNA expression was downregulated by genistein in LNCaP but not C4-2 cells. No other compound tested altered PSA mRNA expression. PSA protein expression was downregulated by genistein, seleno-L-methionine, DL-alpha-tocopherol in LNCaP cells. In C4-2 cells only genistein significantly reduced the secretion of PSA protein.. In the LNCaP progression model PSA expression depends on the compound, its concentration and on the hormonal dependence of the cell line used and does not necessarily reflect cell growth or death. Before potential substances are evaluated in clinical trials using PSA as a surrogate end point marker, their effect on PSA mRNA and protein expression has to be considered to correctly assess treatment response by PSA.

Topics: Adenocarcinoma; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Biomarkers, Tumor; Carotenoids; Cell Line, Tumor; Cell Proliferation; Disease Progression; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Genistein; Humans; Lycopene; Male; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; Selenomethionine; Vitamins

Prostate cancer family history has been associated with increased risk of the malignancy. Most prior studies have been retrospective and subject to recall bias, however, and data evaluating interactions with other important risk factors are limited. We examined the relationship between a family history of prostate cancer and prostate cancer risk in relation to body size, micronutrients and other exposures in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of Finnish male smokers. Family history of cancer information was self-reported once during the study in 1991, and anthropometry was measured by trained personnel. Among 19,652 men with complete data, 1,111 incident cases were identified during up to 12.3 years of follow-up. A first-degree family history of prostate cancer was associated with an overall relative risk (RR) of 1.91 (95% CI = 1.49-2.47) and a RR of 4.16 (95% CI = 2.67-6.49) for advanced disease (stage >or= 3), adjusted for age and trial intervention. Our data also suggest that to some degree, height, body mass index, and serum alpha-tocopherol and beta-carotene modify the family history and prostate cancer association, although the interactions were not statistically significant. Supplementation with vitamin E or beta-carotene did not modify the family history-prostate cancer association. This study provides additional evidence that family history is a significant risk factor for prostate cancer.

Topics: Aged; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Body Mass Index; Body Size; Finland; Follow-Up Studies; Humans; Life Style; Male; Medical History Taking; Middle Aged; Multivariate Analysis; Odds Ratio; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Smoking

Although several mechanisms have been proposed to explain the putative role of beta-carotene in cancer, no studies have investigated a possible influence of beta-carotene on caveolin-1 (cav-1) pathway, an important intracellular signaling deregulated in cancer. Here, different human colon and prostate cancer cell lines, expressing (HCT-116, PC-3 cells) or not (Caco-2, LNCaP cells) cav-1, were treated with varying concentrations of beta-carotene (0.5-30 muM) for different periods of time (3-72 h) and the effects on cell growth were investigated. The results of this study show that (i) beta-carotene acted as a growth-inhibitory agent in cav-1-positive cells, but not in cav-1-negative cells; (ii) in cav-1-positive cells, the carotenoid downregulated in a dose- and time-dependent manner the expression of cav-1 protein and messenger RNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8 and -9; when the carotenoid was removed from culture medium, a progressive increase in cell growth was observed with respect to beta-carotene-treated cells and (iii) the transfection of cav-1 in cav-1-negative cells increased cell sensitivity to beta-carotene by inducing apoptosis. This effect was accompanied by a reduction of both cav-1 and AKT phosphorylation and by an increase of c-myc and beta-catenin expression. Silencing of c-Myc attenuated beta-carotene-induced apoptosis and beta-catenin expression. All together, these data suggest that the modulation of cav-1 pathway by beta-carotene could be a novel mechanism by which the carotenoid acts as a potent growth-inhibitory agent in cancer cells.

Topics: Apoptosis; Base Sequence; beta Carotene; beta Catenin; Caveolin 1; Cell Division; Cell Line, Tumor; Colonic Neoplasms; DNA Primers; Fluorescent Antibody Technique; Gene Silencing; Genes, myc; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Phosphorylation; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

Iron overload may increase prostate cancer risk through stimulation of oxidative stress, and endogenous pro- and antioxidant capabilities, i.e. manganese superoxide dismutase (MnSOD) and myeloperoxidase (MPO), may modify these associations. We investigated this hypothesis in the Carotene and Retinol Efficacy Trial cohort in a nested case-control study. Although there was no association between iron intake and risk overall, there was a suggestion of increased risk of clinically aggressive prostate cancer with higher iron intake [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 0.9-2.0]. Associations were most notable for men with aggressive prostate cancer who were below the median consumption of total fruits and vegetables (OR = 1.8, 95% CI = 1.1-3.2). Associations between MPO -463 G to A genotype (rs2333227) and prostate cancer risk were only noted among men with aggressive cancer, with more than a 2-fold risk reduction among men with AA genotypes (OR = 0.4, 95% CI = 0.2-1.0); MnSOD was not associated with risk overall, but the MnSOD T to C (Val-9Ala, rs4880) polymorphism modified associations between risk of clinically aggressive prostate cancer and dietary iron intake (P for interaction = 0.02). Among aggressive cancer cases with the TT genotype, higher iron intake level was associated with >2-fold increase in risk (OR = 2.3, 95% CI = 1.0-4.9), whereas there was no association among men with CC genotypes (OR = 0.9, 95% CI = 0.4-2.3). Although interactions were not significant, there were similar patterns for MPO genotype, iron intake and risk. These findings suggest that higher iron intake may be associated with risk of clinically aggressive prostate cancer, and that endogenous antioxidant capabilities may modify these associations.

Topics: Administration, Oral; Aged; Alcohol Drinking; beta Carotene; Cohort Studies; Diet; DNA; Genotype; Humans; Iron; Male; Middle Aged; Oxidative Stress; Peroxidase; Prostatic Neoplasms; Reference Values; Risk Factors; Superoxide Dismutase; United States

Both genetic variants and messenger RNA (mRNA) expression of DNA repair and tumor suppressor genes have been investigated as molecular markers for therapy outcome. However, the phenotypic impact of genetic variants often remained unclear, thus the rationale of their use in risk prediction may be limited. We therefore analyzed genetic variants together with anthropometric and lifestyle factors to see how these affect mRNA levels of ERCC1, MDM2 and TP53 in primary blood lymphocytes. mRNA expression was measured in 376 prostate cancer patients by quantitative real-time polymerase chain reaction after reverse transcription, and ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and TP53 rs17878362 (p53PIN3) polymorphisms were determined. Considerable interindividual differences in mRNA expression were found (coefficients of variation: ERCC1, 45%; MDM2, 43% and TP53, 35%). ERCC1 expression was positively correlated with plasma levels of beta-carotene (P = 0.03) and negatively correlated with canthaxanthin (P = 0.02) and lutein (P = 0.02). Overall, the polymorphisms affected mRNA expression only weakly. Carriers of a distinct ERCC1 haplotype (CC) showed, however, significantly lower expression values than non-carriers (P = 0.001). Applying logistic regression, we found that CC haplotype carriers had a 1.69-fold increased odds ratio (95% confidence interval: 1.06-2.71) for reduced ERCC1 mRNA levels. This low ERCC1 expression might be associated with reduced DNA repair and better therapy response. In summary, the association we have found between ERCC1 genotype and mRNA expression supports recent clinical observations that genetic variation in ERCC1 can affect treatment outcome and prognosis. Our study further revealed a modulating effect by nutritional factors.

Topics: Aged; Alcohol Drinking; beta Carotene; Body Mass Index; Canthaxanthin; DNA-Binding Proteins; Endonucleases; Haplotypes; Humans; Lutein; Lymphocytes; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Prostatic Neoplasms; Proto-Oncogene Proteins c-mdm2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Smoking; Tumor Suppressor Protein p53

Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive.. We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions.. No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk.. In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.

Topics: Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Case-Control Studies; Confidence Intervals; Humans; Linear Models; Logistic Models; Lycopene; Male; Mass Screening; Middle Aged; Odds Ratio; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Surveys and Questionnaires

Carotenoids possess antioxidant properties and thus may protect against prostate cancer. Epidemiological studies of dietary carotenoids and this malignancy were inconsistent, partially due to dietary assessment error. In this study, we aimed to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in a population-based case-control study in Arkansas. Cases (n = 193) were men with prostate cancer diagnosed in 3 major hospitals, and controls (n = 197) were matched to cases by age, race, and county of residence. After adjustment for confounders, plasma levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin were inversely associated with prostate cancer risk. Subjects in the highest quartile of plasma lycopene (513.7 microg/l) had a 55% lower risk of prostate cancer than those in the lowest quartile (140.5 microg/l; P trend = 0.042). No apparent association was observed for plasma alpha-carotene and beta-carotene. Further adjustment for the other 4 carotenoids did not materially alter the risk estimates for plasma lycopene, lutein/zeaxanthin, and beta-cryptoxanthin but appeared to result in an elevated risk with high levels of plasma alpha-carotene and beta-carotene. The results of all analyses did not vary substantially by age, race, and smoking status. This study added to the emerging evidence that high circulating levels of lycopene, lutein/zeaxanthin, and beta-cryptoxanthin are associated with a low risk of prostate cancer.

Topics: Antioxidants; Arkansas; beta Carotene; Carotenoids; Case-Control Studies; Cryptoxanthins; Humans; Lutein; Lycopene; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Xanthophylls; Zeaxanthins

Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental beta-carotene was associated with a decreased risk of prostate cancer among men with low baseline plasma beta-carotene levels.. We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.. We identified 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin E use. Supplemental beta-carotene intake at a dose level of at least 2000 microg/day was associated with decreased prostate cancer risk in men with low (below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced prostate cancer was 492 per 100,000 person-years in those who did not take supplemental vitamin E, 153 per 100,000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in those who took supplemental vitamin E for 10 or more years. Among men with low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was 1122 per 100,000 person-years in those who did not take supplemental beta-carotene, and 623 per 100,000 person-years in those who took at least 2000 microg/day of supplemental beta-carotene.. Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and beta-carotene supplementation in men with low dietary beta-carotene intakes were associated with reduced risk of this disease.

Topics: Adult; Aged; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Incidence; Male; Mass Screening; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Smoking; Treatment Outcome; United States; Vitamin E

Topics: Aged; beta Carotene; Beverages; Daucus carota; Family Health; Humans; Male; Prostatic Neoplasms

Lycopene has been associated with reduced prostate cancer risk, although the results of epidemiological studies have varied. We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-control study of prostate cancer in North Carolina. Plasma alpha-tocopherol and beta-carotene levels were measured using high-performance liquid chromatography. XRCC1 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. The final dataset included 77 cases and 174 controls with complete questionnaires, genotyping, and plasma analyses. Among men with the Arg/Arg genotype at codon 399, odds ratios (ORs) for prostate cancer risk associated with medium (732-1,529 microg/day) and high (>1,529 microg/day) lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06-0.71), respectively (P(trend) < 0.01). Similar analyses for persons with Arg/Gln or Gln/Gln genotypes produced null results. Above-median (1,048 microg/day) lycopene intake combined with above-median levels of alpha-tocopherol and beta-carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg genotype but not those with at least one Gln allele (P(interaction) = 0.01). Although limited by small sample size, these findings indicate that the association between lycopene and prostate cancer is complex and may be modified by other antioxidants and by XRCC1 genotype.

Topics: Aged; alpha-Tocopherol; Anticarcinogenic Agents; Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Chromatography, High Pressure Liquid; Codon; Confidence Intervals; DNA-Binding Proteins; Genotype; Humans; Lycopene; Male; Middle Aged; North Carolina; Odds Ratio; Polymorphism, Restriction Fragment Length; Prostatic Neoplasms; Risk Factors; Surveys and Questionnaires; X-ray Repair Cross Complementing Protein 1

Folate is hypothesized to be inversely associated with the risk of several cancers, but such a potential association has not been well studied for prostate cancer. Vitamin B-6, vitamin B-12, methionine, and alcohol can influence folate-related metabolism.. The objective was to investigate the associations between dietary factors of one-carbon metabolism and prostate cancer risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study.. Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated from a 276-item modified dietary history questionnaire. Cox proportional hazard models, adjusted for age and vitamin supplement use, estimated relative risks (RR) and 95% CIs.. Vitamin B-6 intake was inversely associated with prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% CI: 0.72, 1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with significantly increased risk (RR = 1.36; 95% CI: 1.14, 1.96; P for trend = 0.01). No association between folate or alcohol intake and prostate cancer risk was observed. No differences were found in the above associations according to stage of disease or subgroups of several potential effect modifiers.. We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation.

Topics: Aged; Alcohol Drinking; alpha-Tocopherol; beta Carotene; Carbon; Case-Control Studies; Dietary Supplements; Double-Blind Method; Ethanol; Finland; Folic Acid; Humans; Male; Methionine; Middle Aged; One-Carbon Group Transferases; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Smoking; Vitamin B 12; Vitamin B 6

Greater adult height, which reflects a combination of early nutrition, exposure to androgens, growth hormones, and other factors during growth and development, as well as heredity, has been associated with increased prostate cancer risk in several observational studies, but findings have been inconsistent. We examined this relationship in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline, 29,119 Finnish male smokers 50 to 69 years old had height and weight measured by trained personnel, provided information on demographic, smoking, medical, and other characteristics, and completed an extensive diet history questionnaire. A total of 1,346 incident prostate cancer cases were identified during a follow-up period of up to 17.4 years (median, 14.1 years). In age-adjusted Cox proportional hazards models, the hazard ratios and 95% confidence intervals for prostate cancer according to increasing quintiles of height [178 cm] were 1.00 (reference), 1.11 (0.93-1.32), 1.11 (0.95-1.31), 1.30 (1.01-1.55), and 1.14 (0.96-1.35); P(trend) = 0.04. In analyses stratified by disease stage (available for 916 cases), a strong dose-response relationship was observed between greater height and advanced, but not earlier-stage, disease [tumor-node-metastasis stage III-IV, hazard ratio and 95% confidence interval for increasing quintiles of height: 1.77 (1.18-2.65), 1.82 (1.25-2.65), 1.93 (1.29-2.90), and 2.02 (1.37-2.97); P(trend) = 0.0008, P(interaction) = 0.002]. Our study provides additional evidence that increased height is a risk factor for prostate cancer and suggests that taller men are particularly susceptible to advanced disease.

Topics: Aged; alpha-Tocopherol; beta Carotene; Body Height; Cohort Studies; Follow-Up Studies; Growth Hormone; Humans; Male; Middle Aged; Neoplasm Metastasis; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors

Oxidative stress may enhance prostatic carcinogenesis. A polymorphism [valine (V) --> alanine (A)] of manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, has been recently associated with prostate cancer. We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels (selenium, lycopene, and alpha-tocopherol) and beta-carotene treatment among 567 cases and 764 controls nested in the prospective Physicians' Health Study. We found little overall association between MnSOD polymorphism and prostate cancer risk; however, this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants (P(interaction) > or = 0.05). Among men with the AA genotype, high selenium level (4th versus 1st quartile) was associated with a relative risk (RR) of 0.3 [95% confidence interval (CI), 0.2-0.7] for total prostate cancer; for clinically aggressive prostate cancer, the RR was 0.2 (95% CI, 0.1-0.5). In contrast, among men with the VV/VA genotype, the RRs were 0.6 (0.4-1.0) and 0.7 (0.4-1.2) for total and clinically aggressive prostate cancer. These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status. Men with AA genotype who were randomly assigned to beta-carotene treatment (versus placebo) had a RR of 0.6 (95% CI, 0.2-0.9; P(interaction) = 0.03) for fatal prostate cancer, but no significant association was observed in men with the VV/VA genotype. Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Genetic Predisposition to Disease; Humans; Lycopene; Male; Middle Aged; Polymorphism, Genetic; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Selenium; Superoxide Dismutase

Biomarkers of trans-fatty acid consumption have been associated with increased risks of breast and colon cancer, although no studies have examined their associations with prostate cancer risk. Using data from the beta-Carotene and Retinol Efficacy Trial, this nested case-control study examined the relationships between serum phospholipid trans-fatty acids and prostate cancer incidence in 272 case and 426 control men. Trans-fatty acids were measured using organic extraction followed by separations with TLC and gas chromatography. Adjusted odds ratios for risk of prostate cancer with increasing levels of trans-fatty acids were calculated using logistic regression. There were consistent trends for increasing prostate cancer risk with higher levels of C18 but not C16 trans-fatty acids, although only trends for Delta11t 18:1 trans-vaccenic and Delta9c,12t 18:2 fatty acids reached statistical significance. Odds ratios (95% confidence interval) contrasting low versus high quartiles for these fatty acids were 1.69 (1.03-2.77) and 1.79 (1.02-3.15), respectively. There were no consistent differences in associations between low-grade and high-grade cancer among the subset of 209 cases with information on tumor grade. Additional studies are needed to confirm these findings and better control for factors, such as use of prostate-specific antigen screening, which may confound this association.

Topics: Aged; beta Carotene; Biomarkers, Tumor; Case-Control Studies; Endpoint Determination; Fatty Acids; Humans; Logistic Models; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin A

It was shown that high doses of beta-carotene (>30 microM) decrease proliferation of prostate cancer cells in vitro. However, it is rather doubtful whether such concentration of beta-carotene is really accessible at cellular level. We studied the effect of 3 and 10 microM beta-carotene on proliferation and gene expression in LNCaP and PC-3 prostate cancer cell lines. Beta-carotene--more efficiently absorbed from medium by androgen-sensitive LNCaP cells--increased proliferation of LNCaP cells whereas it had weaker effect on PC-3 cells. Initial global analysis of expression of genes in both cell lines treated with 10 microM beta-carotene (Affymetrix HG-U133A) showed remarkable differences in number of responsive genes. Their recognition allows for conclusion that differences between prostate cancer cell lines in response to beta-carotene treatment are due to various androgen sensitivities of LNCaP and PC-3 cells. Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).

Topics: Androgens; Apoptosis; beta Carotene; Blotting, Western; Cell Division; Cell Line, Tumor; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Male; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Prostatic Neoplasms; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Signal Transduction

Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alpha-reductase and decrease the clinical symptoms of BPH. Epidemiologic studies report that carotenoids such as lycopene may inhibit prostate cancer. In this investigation the effect of the carotenoid astaxanthin, and SPLE were examined for their effect on 5alpha-reductase inhibition as well as the growth of prostatic carcinoma cells in vitro. These studies support patent #6,277,417 B1. The results show astaxanthin demonstrated 98% inhibition of 5alpha-reductase at 300 microg/mL in vitro. Alphastat, the combination of astaxanthin and SPLE, showed a 20% greater inhibition of 5alpha-reductase than SPLE alone n vitro. A nine day treatment of prostatic carcinoma cells with astaxanthin in vitro produced a 24% decrease in growth at 0.1 mcg/mL and a 38% decrease at 0.01 mcg/mL. SPLE showed a 34% decrease at 0.1 mcg/mL.. Low levels of carotenoid astaxanthin inhibit 5alpha-reductase and decrease the growth of human prostatic cancer cells in vitro. Astaxanthin added to SPLE shows greater inhibition of 5alpha-reductase than SPLE alone in vitro.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgen Antagonists; beta Carotene; Cell Line, Tumor; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; In Vitro Techniques; Male; Plant Extracts; Prostatic Hyperplasia; Prostatic Neoplasms; Serenoa; Xanthophylls

Topics: Adult; beta Carotene; Carcinogens; Carotenoids; Female; France; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Research Design; Smoking; United States

Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of > or =7, n = 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of alpha-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.

Topics: Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Chromatography, High Pressure Liquid; Cryptoxanthins; Disease Progression; Humans; Isomerism; Lutein; Lycopene; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Xanthophylls; Zeaxanthins

Fucoxanthin, a major carotenoid in edible brown algae, potentially inhibits the proliferation of human prostate cancer cells via apoptosis induction. However, it has been postulated that dietary fucoxanthin is hydrolyzed into fucoxanthinol in the gastrointestinal tract before absorption in the intestine. In the present study, we investigated the further biotransformation of orally administered fucoxanthin and estimated the cytotoxicity of fucoxanthin metabolites on PC-3 human prostate cancer cells. After the oral administration of fucoxanthin in mice, two metabolites, fucoxanthinol and an unknown metabolite, were found in the plasma and liver. The unknown metabolite was isolated from the incubation mixture of fucoxanthinol and mouse liver preparation (10,000 g supernatant of homogenates), and a series of instrumental analyses identified it as amarouciaxanthin A [(3S,5R,6'S)-3,5,6'-trihydroxy-6,7-didehydro-5,6,7',8'-tetrahydro-beta,epsilon-carotene-3',8'-dione]. The conversion of fucoxanthinol into amarouciaxanthin A was predominantly shown in liver microsomes. This dehydrogenation/isomerization of the 5,6-epoxy-3-hydroxy-5,6-dihydro-beta end group of fucoxanthinol into the 6'-hydroxy-3'-oxo-epsilon end group of amarouciaxanthin A required NAD(P)+ as a cofactor, and the optimal pH for the conversion was 9.5 to 10.0. Fucoxanthinol supplemented to culture medium via HepG2 cells was also converted into amarouciaxanthin A. The 50% inhibitory concentrations on the proliferation of PC-3 human prostate cancer cells were 3.0, 2.0, and 4.6 microM for fucoxanthin, fucoxanthinol, and amarouciaxanthin A, respectively. To our knowledge, this is the first report on the enzymatic dehydrogenation of a 3-hydroxyl end group of xanthophylls in mammals.

Topics: Administration, Oral; Animals; Antineoplastic Agents; beta Carotene; Cell Division; Cell Line, Tumor; Humans; In Vitro Techniques; Male; Mice; Microsomes, Liver; Prostatic Neoplasms; Xanthophylls

Topics: beta Carotene; Blindness; Clinical Trials as Topic; Contraindications; Dietary Supplements; Drug Labeling; Humans; Lung Neoplasms; Macular Degeneration; Male; Prostatic Neoplasms; Smoking; Zinc

In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.. To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.. Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.. Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.. Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.. The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Cause of Death; Dietary Supplements; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Smoking

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk.. Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic.. Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02).. These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Case-Control Studies; Finland; Genotype; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Superoxide Dismutase

Results of a randomized controlled trial have suggested a protective effect of selenium against prostate cancer. Few other prospective studies have been conducted to confirm or refute this. The association between prostate cancer and baseline toenail selenium level was evaluated in the Netherlands Cohort Study, conducted among 58,279 men, aged 55-69 years at entry. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 6.3 years of follow-up, 540 incident prostate carcinoma cases and 1,211 subcohort members with complete toenail selenium data were available for case-cohort analyses. In multivariate survival analysis, an inverse association between toenail selenium level and prostate cancer risk was observed. Incidence rate ratios in increasing selenium quintiles were 1.00 (ref), 1.05, 0.69, 0.75, and 0.69 (95% confidence interval, 0.48-0.99), respectively (P-trend=0.008). This association persisted after exclusion of cases diagnosed during early follow-up. The inverse association was more pronounced in ex-smokers than current smokers, and unclear in never-smokers. Analysis of effect modification by intake of antioxidant vitamins C, E, and the carotenoids alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin showed a strong, significant interaction with beta-cryptoxanthin, and to a lesser extent with vitamin C. These results confirm the hypothesis that higher selenium intake may reduce prostate cancer risk. Future research on optimum dose level is needed.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Cryptoxanthins; Follow-Up Studies; Humans; Lycopene; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Prostatic Neoplasms; Risk Factors; Selenium; Smoking; Surveys and Questionnaires; Vitamin E; Xanthophylls

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Biological Evolution; Carcinogens; Carotenoids; Disease Models, Animal; Humans; Lung Neoplasms; Lycopene; Male; Prostatic Neoplasms; Rats; Solanum lycopersicum

The roles of retinol, vitamins C and E, and carotenoids as risk factors for prostate carcinoma are still questionable. We evaluated these in the Netherlands Cohort Study.. The cohort study consisted of 58,279 men ages 55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intakes of retinol, vitamins C and E, and several carotenoids were measured by means of a 150-item semi-quantitative food-frequency questionnaire.. In multivariate analyses a positive association with prostate cancer risk was observed for intake of beta-cryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94, 1.01, 1.16, 1.41; p-trend < 0.01. For intake of retinol, vitamins C and E and other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for vitamin supplement use were decreased, but not significantly. Among nondrinkers, nonsignificant inverse associations were observed for intake of retinol, alpha-carotene, and beta-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60, and 0.76, respectively). Among drinkers, beta-cryptoxanthin was positively associated (RR highest vs lowest quintile = 1.40).. These data show a positive association between beta-cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol, alpha-carotene, and beta-carotene among nondrinkers; this suggests an interaction between vitamins and alcohol consumption, which needs confirmation. Lycopene was not associated with prostate cancer.

Topics: Aged; Alcohol Drinking; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Confidence Intervals; Cryptoxanthins; Feeding Behavior; Humans; Male; Middle Aged; Multivariate Analysis; Netherlands; Prospective Studies; Prostatic Neoplasms; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamin E; Xanthophylls

Topics: Aged; beta Carotene; Beverages; Daucus carota; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Although dietary intake of tomatoes and tomato products containing lycopene has been reported to reduce the risk of prostate cancer, few studies have been done on the relationship between plasma lycopene and other carotenoids and prostate cancer. This case-control study was conducted to investigate the effects of plasma lycopene, other carotenoids, and retinol, as well as alpha- and gamma-tocopherols on the risk of prostate cancer. The study included 65 patients with prostate cancer and 132 cancer-free controls; all of them were interviewed using a standard epidemiological questionnaire at the Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Plasma levels of carotenoids, retinol, and tocopherols were measured by high performance liquid chromatography. An unconditional logistic regression model was used in bivariate and multivariate analyses using Statistical Analysis System (SAS). After adjusting for age, race, years of education, daily caloric intake, pack-years of smoking, alcohol consumption, and family history of prostate cancer, significantly inverse associations with prostate cancer were observed with plasma concentrations of the following carotenoids: lycopene [odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.78; P for trend, 0.0052] and zeaxanthin (OR, 0.22; 95% CI, 0.06-0.83; P for trend, 0.0028) when comparing highest with lowest quartiles. Borderline associations were found for lutein (OR, 0.30; 95% CI, 0.09-1.03; P for trend, 0.0064) and beta-cryptoxanthin (OR, 0.31; 95% CI, 0.08-1.24; P for trend, 0.0666). No obvious associations were found for alpha- and beta-carotenes, retinol, and alpha- and gamma-tocopherols. Our study confirmed the inverse associations between lycopene, other carotenoids such as zeaxanthin, lutein, and beta-cryptoxanthin, and prostate cancer. This study provides justification for further research on the associations between lycopene and other antioxidants and the risk of prostate cancer.

Topics: Adult; beta Carotene; Carotenoids; Case-Control Studies; Cryptoxanthins; Humans; Lutein; Lycopene; Male; Middle Aged; Odds Ratio; Prostatic Neoplasms; Risk Factors; Xanthophylls; Zeaxanthins

Topics: Antioxidants; beta Carotene; Daucus carota; Evidence-Based Medicine; Humans; Male; Phytotherapy; Prostatic Neoplasms

Topics: Antioxidants; beta Carotene; Evidence-Based Medicine; Humans; Male; Prostatic Neoplasms

Topics: Antioxidants; beta Carotene; Diet; Dietary Supplements; Humans; Male; Prostatic Neoplasms

Epidemiologic and animal studies provide support for a relationship between high intakes of carotenoids from fruits and vegetables with reduced risk of several malignancies including prostate cancer. The highly controlled environments of in vitro systems provide an opportunity to investigate the cellular and molecular effects of carotenoids. The effects of beta-carotene (BC) on in vitro growth rates, p21(WAF1) and p53 gene expression, as well as the conversion of BC to retinol were investigated in three human prostate adenocarcinoma cell lines: PC-3, DU 145 and LNCaP. In these experiments, media concentrations of 30 micromol BC/L for 72 h significantly (P < 0.05) slowed in vitro growth rates in all three cell lines, independently of p53 or p21(WAF1) status or expression. (14)C-labeled retinol was detected in prostate tumor cells incubated with (14)C-labeled BC, suggesting metabolic conversion of BC to retinol. Conversely, no (14)C-labeled retinol was detected in media incubated without prostate cancer cells. These studies support a hypothesis that in vitro biological effects of BC on prostate cells may result in part from the conversion of BC to retinol or other metabolites. The possibility that prostate cancer cells in vivo locally metabolize provitamin A carotenoids to retinol and other related metabolites may have implications for our understanding of prostate cancer etiology and the design of future prevention studies.

Topics: Adenocarcinoma; beta Carotene; Cell Division; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Humans; Intracellular Fluid; Male; Prostatic Neoplasms; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Vitamin A

Cell culture systems provide an opportunity to evaluate the effects of carotenoids on molecular and cellular processes involved in proliferation and differentiation of prostate cancer cells. The stability and cellular uptake of beta-carotene (BC) by prostate cancer cells were investigated in vitro by use of various delivery methods and three human prostate adenocarcinoma cell lines: PC-3, DU 145, and LNCaP. Recovery of BC from the media (prepared from water-dispersible BC beadlets) significantly (p < 0.05) decreased after 12 hours in culture and continued to significantly decrease (p < 0.05) after 24, 48, 72, and 96 hours, an observation primarily attributed to BC degradation rather than isomerization, metabolism, or cellular uptake. The uptake of BC by prostate cancer cells was compared when delivered by tetrahydrofuran, BC-enriched bovine serum, water-dispersible BC beadlets, and artificial liposomes. Recovery of BC after three days in culture from enriched bovine serum medium was significantly (p < 0.05) greater than recovery from medium prepared by beadlets, tetrahydrofuran, or artificial liposomes. We conclude that BC is relatively unstable in vitro and that degradation products may contribute to biological responses. Furthermore, our studies indicate that enriched bovine serum provides a stable and physiological approach to carotenoid treatment of cells in culture.

Topics: Adenocarcinoma; Animals; beta Carotene; Cattle; Culture Media; Drug Delivery Systems; Drug Stability; Furans; Humans; In Vitro Techniques; Lipoproteins; Liposomes; Male; Microspheres; Pharmaceutical Vehicles; Prostatic Neoplasms; Solvents; Time Factors; Tumor Cells, Cultured

Topics: Anticarcinogenic Agents; Antioxidants; beta Carotene; Carotenoids; Diet; Humans; Lycopene; Male; Mass Screening; Nutritional Physiological Phenomena; Prostatic Neoplasms; Selenium; Solanum lycopersicum; Vitamin E

Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent pr

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Aspirin; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Double-Blind Method; Humans; Lycopene; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors

Dietary intake of tomatoes and tomato products containing lycopene, an antioxidant carotenoid, has been shown in recent studies to reduce the risk of cancer. This study was conducted to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and their controls. Serum lipid and protein oxidation was also measured. Twelve prostate cancer patients and 12 age-matched subjects were used in the study. Significantly lower serum and tissue lycopene levels (44%, p = 0.04; 78%, p = 0.050, respectively) were observed in the cancer patients than in their controls. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups (p = 0.395 and p = 0.280, respectively). Although there was no difference (p = 0.760) in serum lipid peroxidation between cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/- 0.56 mumol/l, respectively), serum protein thiol levels were significantly lower among the cancer patients (p = 0.026). This study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing the risk of prostate cancer needs to be evaluated in future studies.

Topics: Aged; Antioxidants; beta Carotene; Biomarkers; Blood Proteins; Carotenoids; Case-Control Studies; Humans; Lipid Peroxidation; Lycopene; Male; Middle Aged; Oxidation-Reduction; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Antioxidants; beta Carotene; Carotenoids; Case-Control Studies; Clinical Trials as Topic; Diet; Humans; Lycopene; Male; Phytotherapy; Prostatic Neoplasms; Risk; Selenium; Smoking; Solanum lycopersicum; Vitamin E

Topics: Anticarcinogenic Agents; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Humans; Lycopene; Male; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin E

Topics: Ascorbic Acid; beta Carotene; Follow-Up Studies; Humans; Incidence; Male; Proportional Hazards Models; Prostatic Neoplasms; Reproducibility of Results; Risk Factors; Time Factors

Beta-carotene, canthaxanthin and retinoic acid (RA) inhibited growth of human DU145 prostate cancer cells by 45, 56 and 18%, respectively. Lycopene was also found to inhibit cell growth. Other carotenoids including xanthophyll (lutein), cryptoxanthin and zeaxanthin were less effective. Liarozole (a novel imidazole-derived inhibitor of intracellular RA catabolism) had a modest effect upon cell growth, this drug significantly amplified the pro-apoptotic actions of beta-carotene and RA. RA-induced expression of thymosin beta-10, an apoptotic accelerant, was associated with increased nuclear DNA nicking as measured using TUNEL. Liarozole enhanced the proapoptotic actions of RA upon DNA fragmentation in a dose-dependent manner. These actions were accompanied by inhibition of the cell survival factor bcl-2. Liarozole may thus prove useful as a novel chemotherapeutic/chemopreventive agent by boosting retinoid-induced apoptosis in the prostate.

Topics: Antineoplastic Agents; Apoptosis; beta Carotene; Blotting, Northern; Cell Division; DNA Fragmentation; Drug Synergism; Genes, bcl-2; Humans; Imidazoles; Male; Prostatic Neoplasms; Retinoids; RNA, Messenger; Thymosin; Tretinoin; Tumor Cells, Cultured

Dietary factors are likely candidates for important determinants of prostatic cancer risk. Among the most investigated nutritional factors have been antioxidants. We evaluated dietary beta-carotene and vitamin C in relation to subsequent risk of prostate cancer in a prospective study of 1,899 middle-aged men. We combined prostate cancer cases diagnosed in the first 24 years of follow-up with incident cases identified from the Health Care Financing Administration hospitalization and outpatient files during an additional 6-year follow-up period. We obtained death certificates for all decedents. During the 30-year follow-up, prostate cancer developed in 132 men. There was no indication that consumption of beta-carotene or vitamin C was related to increased or decreased risk of prostate cancer. Relative risks for highest vs lowest quartiles of beta-carotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75-2.14] and 1.03 (95% CI = 0.59-1.60), respectively, after adjustment for age, number of cigarettes smoked per day, dietary cholesterol and saturated fat, alcohol consumption, total energy intake, and occupation. Associations between intake of these nutrients and risk of prostate cancer differed depending on whether the cancer was diagnosed during the first 19 years of follow-up or the next 11 years of follow-up. Overall survival over the 30 years of follow-up was positively associated with intake of beta-carotene and vitamin C.

Topics: Adult; Ascorbic Acid; beta Carotene; Diet; Health Behavior; Humans; Illinois; Incidence; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Socioeconomic Factors

An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity. Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer. The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated. Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively. Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g. The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue. No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed. In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins. Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g. We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C30 reversed phase column. All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues. cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks. We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual v

Topics: Aged; Anticarcinogenic Agents; Antioxidants; beta Carotene; Biomarkers; Carotenoids; Chromatography, High Pressure Liquid; Diet; Humans; Lycopene; Male; Middle Aged; Prostate; Prostatic Neoplasms; Risk Factors; Vitamin A

The relationship between risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Ontario, Canada. Cases were men with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992. Controls were selected randomly from assessment lists maintained by the Ontario Ministry of Revenue, and were frequency-matched to the cases on age. The study included 207 cases (51.4 percent of those eligible) and 207 controls (39.4 percent of those eligible), and information on dietary intake was collected from them by means of a quantitative diet history. There was a positive association between energy intake and risk of prostate cancer, such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk. In contrast, there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk. There was some evidence for an inverse association with saturated fat intake, although the dose-response pattern was irregular. There was a weak (statistically nonsignificant) positive association between polyunsaturated fat intake and risk of prostate cancer. Relatively high levels of retinol intake were associated with reduced risk, but there was essentially no association between dietary beta-carotene intake and risk. There was no alteration in risk in association with dietary fiber, cholesterol, and vitamins C and E. Although these patterns were evident both overall and within age-strata, and persisted after adjustment for a number of potential confounding factors, they could reflect (in particular) the effect of nonrespondent bias.

Topics: Adenocarcinoma; Aged; beta Carotene; Carotenoids; Case-Control Studies; Diet; Dietary Fats; Energy Intake; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin A

Topics: Antineoplastic Agents; beta Carotene; Calcitriol; Carotenoids; Food, Fortified; Humans; Male; Prostatic Neoplasms

Topics: Aged; beta Carotene; Carotenoids; Diet; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin A

This is a further analysis of a case-control study of 452 prostate cancer cases and 899 population controls that was conducted in 1970-1983 among the multiethnic population of Hawaii. Because a previous analysis had shown a positive association with intake of beta-carotene, a nutrient presently being tested for chemoprevention, the authors reexamined the data for consistency among the main food sources of beta-carotene. Vegetables and fruits containing other phytochemicals suspected to be cancer inhibitors were also examined. With the exception of papaya, which was positively associated with risk among men aged 70 years and older, consumption of other yellow-orange fruits and vegetables, tomatoes, dark green vegetables, and cruciferous vegetables was not associated with prostate cancer risk. These results suggest that: 1) the positive association with beta-carotene intake among older men that the authors previously reported was essentially due to the greater papaya consumption of cases compared with controls; and 2) intake of beta-carotene, lycopene, lutein, indoles, phenols, or other phytochemicals is not associated with prostate cancer risk.

Topics: Aged; beta Carotene; Carotenoids; Case-Control Studies; Fruit; Hawaii; Humans; Male; Prostatic Neoplasms; Risk Factors; Vegetables

A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for prostate cancer were significantly elevated among cigarette smokers (relative risk, 1.8; 95% confidence interval, 1.1-2.9) and users of smokeless tobacco (relative risk, 2.1; 95% confidence interval, 1.1-4.1). No significant associations were found with frequency of consumption of meats, dairy products, fruits, or vegetables. There were no overall significant associations between consumption of vitamin A from animal sources (retinol) and provitamin A from plant sources (carotene) and risk, but positive trends were seen for ages under 75, while inverse associations were found at older ages. Beverage consumption, including drinking coffee and alcohol, was unrelated to risk. Marital status, education, rural/urban status, and farming residence were also unrelated to the risk of fatal prostate cancer. The findings add to limited evidence that tobacco may be a risk factor for prostate cancer, but fail to provide clues to dietary or other risk factors.

Topics: Adult; Aged; Alcoholic Beverages; beta Carotene; Carotenoids; Coffee; Cohort Studies; Diet; Humans; Male; Middle Aged; Nicotiana; Plants, Toxic; Prostatic Neoplasms; Risk Factors; Smoking; Vitamin A

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.

Topics: Aged; beta Carotene; Carotenoids; Case-Control Studies; Diet; Humans; Lycopene; Male; Middle Aged; Prostatic Neoplasms; Retinol-Binding Proteins; Risk; Vitamin A; Vitamin E

A case-control study of 371 prostate cancer patients and comparable control subjects admitted to Roswell Park Memorial Institute (RPMI), Buffalo, New York, was conducted. Data were obtained from routine epidemiologic questionnaires administered to all patients on admission. An index of beta-carotene intake was computed based on the vitamin A activity of 27 fruits and vegetables included in a food frequency checklist. A similar measure of fat intake from meats was computed based on nine meats included in the checklist. Intake frequencies of common and alcoholic beverages also were studied. A significant age-adjusted and residence-adjusted protective effect for high levels of beta-carotene intake was observed (relative risk [RR], 0.60; 95% confidence interval [CI], 0.37 to 0.99). This effect was evident particularly among men 68 years of age and younger (RR, 0.30; 95% CI, 0.13 to 0.66), but not among subjects older than 68 years of age. A trend toward increased risk for fat intake was not significant. However, the reported usual consumption of high-fat milk was associated with increased risk (RR, 1.92; 95% CI, 1.05 to 3.50). A greater reported frequency of whole milk intake was similarly associated with increased risk. Men who reported drinking three or more glasses of whole milk daily had an RR of 2.49 (95% CI, 1.27 to 4.87), compared with men who reported never drinking whole milk. When these findings are evaluated in the context of other recent studies, the weight of the evidence appears to favor the hypothesis that animal fat intake is related to increased risk of prostate cancer.

Topics: Aged; beta Carotene; Carotenoids; Dietary Fats; Epidemiologic Methods; Humans; Male; New York; Prostatic Neoplasms; Risk; Risk Factors

One hundred patients with prostate cancer and two different control series [100 benign prostatic hyperplasia (BPH) patients and 100 general hospital patients] were matched to each other upon hospital admittance, age (+/- 3 years) and date of admission (+/- 3 months), and directly interviewed during admission from 1981 to 1984 in Kyoto, Japan. Major dietary findings derived from a quantitative food frequency technique for estimating usual diet are as follows. (a) The smaller the dietary intake of beta-carotene and vitamin A as well, the higher the risk, with a highly significant linear trend. From the beta-carotene analyses, the relative risk (95% confidence interval) for the lowest intake quartile relative to the highest was 2.10 (0.98-4.47) for the uncorrected intake, 2.35 (1.08-5.12) for the intake per kg, and 2.94 (1.34-6.44) for the intake per kcal in the comparison with BPH patients; 2.88 (1.31-6.32), 2.56 (1.14-5.76), and 3.50 (1.52-8.06), respectively, in the comparison with hospital controls. The corresponding relative risk obtained from the vitamin A analyses was 2.82 (1.30-6.14), 2.64 (1.24-5.60), and 3.29 (1.47-7.35) in due order in the comparison with BPH patients; 2.69 (1.22-5.94), 4.78 (1.98-11.52), and 3.50 (1.52-8.06) in the comparison with hospital controls. (b) beta-Carotene as well as vitamin A contained in green/yellow vegetables were significantly protective, and those in seaweeds and kelp suggestively protective. But those in fruits appeared to enhance the risk. (c) The risk reduction by dietary beta-carotene and vitamin A was significant in the older men (70-79 years), but not in the younger men (50-69 years). (d) Total energy intake and the dietary intake of fat, protein, carbohydrate, water, fiber, ash, such vitamins as retinol, B1, B2, C, and niacin, and such minerals as calcium, potassium, sodium, phosphorus, and iron were not linked with prostate cancer risk. (e) A protective effect of dietary beta-carotene and vitamin A against prostate cancer could be related to the low overall fat intake in Japan.

Topics: Age Factors; Aged; beta Carotene; Carotenoids; Diet; Dietary Fats; Energy Intake; Humans; Japan; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors; Vitamin A

Levels of retinol, beta carotene, and alpha tocopherol were assayed by high performance liquid chromatography (HPLC) in serum from subjects with clinical prostatic cancer (n = 94), focal prostatic cancer (n = 40), benign prostatic hyperplasia (n = 130), and from hospital controls (n = 130). Levels of beta carotene and alpha tocopherol varied for prostatic cancer patients by disease stage and by the period in the treatment sequence when blood was collected. This made any assessment of their association with prostatic cancer risk difficult. The mean level of serum retinol was significantly lower (P less than 0.05) in prostatic cancer patients than in the controls. For serum retinol this difference did not appear to be attributable to age, stage of disease, period in which the blood was collected, or to several other potentially confounding factors. When the serum retinol level was considered in quintile classes, there was a statistically significant (P less than 0.05) trend of increased prostatic cancer risk associated with decreasing serum retinol levels.

Topics: Age Factors; Aged; beta Carotene; Carotenoids; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin E

A case-control study of prostatic cancer which consisted of 100 patients with prostatic cancer, matched for hospital, age (+/- 3 yr) and hospital admission date (+/- 3 months) to patients with benign prostatic hyperplasia (BPH) and hospital controls, was conducted from 1981 to 1984. Low daily intake of beta-carotene (RR = 2.13: 95% confidence interval, 1.20-3.77) and of vitamin A (RR = 1.94: 1.10-3.43), as compared to the intake of those substances by BPH controls, were factors significantly correlated with the development of prostatic cancer. Low daily intake of beta-carotene (RR = 2.13: 1.20-3.77), as compared with hospital controls, were significantly correlated with prostatic cancer development. Infrequent intake of bread (RR = 2.40: 1.31-4.38), intended to represent a westernized diet, and of spinach (RR = 1.96: 1.01-7.73), a typical green and yellow vegetable, as compared to BPH controls and infrequent intake of spinach (RR = 4.55: 1.82-11.11) as compared to by hospital controls, were significant risk factors for prostatic cancer. Intake of carbohydrates, protein, fat, total calories, fibers, vitamin B and vitamin C were not correlated with the development of prostatic cancer.

Topics: Aged; Basidiomycota; beta Carotene; Bread; Carotenoids; Diet; Humans; Japan; Male; Middle Aged; Nutritional Physiological Phenomena; Prostatic Neoplasms; Risk Factors; Vitamin A