beta-carotene and Pancreatic-Neoplasms

We conducted a meta-analysis to systematically evaluate the association between antioxidants intake and pancreatic cancer risk. Relevant articles were retrieved from PUBMED and EMBASE databases and standard meta-analysis methods were applied. Finally a total of 18 studies were included. Comparing the highest with lowest categories, higher dietary intakes of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin were significantly associated with reduced pancreatic cancer risk (for selenium, pooled OR = 0.47, 95%CI 0.26-0.85; for vitamin C, pooled OR = 0.68, 95%CI 0.57-0.80; for vitamin E, pooled OR = 0.70, 95%CI 0.62-0.81; for β-carotene, pooled OR = 0.74, 95%CI 0.56-0.98; for β-cryptoxanthin, pooled OR = 0.70, 95%CI 0.56-0.88). Lycopene intake was marginally associated with pancreatic cancer risk (pooled OR = 0.85, 95%CI 0.73-1.00), while no significant association was observed for α-carotene, lutein and zeaxanthin. In summary, higher dietary intake of selenium, vitamin C, vitamin E, β-carotene and β-cryptoxanthin was inversely associated with pancreatic cancer risk.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Beta-Cryptoxanthin; Carotenoids; Databases, Factual; Diet; Humans; Lutein; Lycopene; Pancreatic Neoplasms; Risk Factors; Selenium; Vitamin E; Zeaxanthins

Pancreatic cancer has a poor prognosis and is often diagnosed at an advanced stage, which makes it difficult to treat. The low survival rate of patients with pancreatic cancer points towards an increased need for novel therapeutic and chemopreventive strategies and also early detection of this disease. Increased consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer. Synthetic and natural, diet-derived bioactive compounds have been evaluated as pancreatic cancer chemopreventive agents and have demonstrated various degrees of efficacy in cellular and in vivo animal models. Some chemopreventive agents (for example, curcumin or resveratrol) have also been reported to sensitize pancreatic cancer cells to standard chemotherapeutic drugs (for example, gemcitabine or erlotinib), which suggests that chemopreventive agents could potentially be used as potentiators of standard chemotherapy. Few clinical trials of pancreatic cancer chemopreventive agents have been completed and some are in early phases. Further development of pancreatic cancer chemopreventive agents may prove to be tremendously valuable for individuals at high risk of developing pancreatic cancer and patients who present with premalignant lesions. This Review discusses the current state of the pancreatic cancer chemoprevention field and highlights the challenges ahead.

Topics: Alkyl and Aryl Transferases; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Camellia sinensis; Celecoxib; Cell Transformation, Neoplastic; Chemoprevention; Curcumin; Cyclooxygenase 2 Inhibitors; Deoxycytidine; Disease Models, Animal; Down-Regulation; Drug Synergism; Gemcitabine; Humans; Isothiocyanates; Pancreatic Neoplasms; Phototherapy; Pyrazoles; Sulfonamides; Tea; Vitamin D; Vitamin E

Aspirin and other NSAIDs are showing promise in the chemoprevention of colorectal cancer. Ongoing trials will eventually provide still lacking information about the optimum dose and treatment duration. NSAIDs may also help to lower the risk of cancer in other organs such as the oesophagus, and possibly breast, stomach, and lung. The chemoprevention by NSAIDs should be seen not as the sole method of prevention, but as an additional tool which will be accompanied by other approaches such as stopping smoking, limiting alcohol consumption, and eating more fruits and vegetables. The chemoprevention by NSAIDs needs also to be balanced against the risks of toxicity (particularly in the stomach) and the other beneficial effects such as prevention of cardiovascular morbidity and mortality. Some of the NSAID induced gastric ulceration and bleeding will most likely be avoided by adopting the use of cyclooxygenase-2 (COX-2) selective NSAIDs, which will selectively inhibit COX-2 while sparing COX-1.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; beta Carotene; Case-Control Studies; Child; Cohort Studies; Colorectal Neoplasms; Cricetinae; Cyclooxygenase Inhibitors; Esophageal Neoplasms; Humans; Neoplasms; Pancreatic Neoplasms; Prospective Studies; Prostaglandin Antagonists; Prostaglandins; Randomized Controlled Trials as Topic; Skin Neoplasms; Stomach Neoplasms; Time Factors

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.

Topics: Adolescent; Adult; Alcohol Drinking; Animals; beta Carotene; Breast Neoplasms; Case-Control Studies; Female; Folic Acid; Follow-Up Studies; Hematinics; Humans; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasms; Odds Ratio; Pancreatic Neoplasms; Postmenopause; Premenopause; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Risk; Risk Factors; Smoking; Time Factors; Vitamins

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50-69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow-up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two-sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09-1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01-2.43, p-trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19-1.79 highest quartile OR = 2.92, 95% CI = 1.47-5.77, p-trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85-1.22; highest quartile OR = 1.04, 95% CI = 0.60-1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.

Topics: Aged; alpha-Tocopherol; beta Carotene; Case-Control Studies; Humans; Logistic Models; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Risk Factors; Smoking; Telomere Homeostasis

Many epidemiologic studies have examined the association between C-reactive protein (CRP) and risk of cancer with inconsistent results.. We conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to test whether prediagnostic circulating CRP concentrations were associated with pancreatic adenocarcinoma. Between 1985 and 2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in PLCO. Controls (n = 510 in ATBC, n = 374 in PLCO) were alive at the time the case was diagnosed and were matched by age, date of blood draw, sex, and race. We used conditional logistic regression adjusted for smoking to calculate OR and 95% CI for pancreatic cancer.. CRP concentrations (ng/mL) tended to be inversely or not associated with pancreatic cancer risk in ATBC, PLCO, and combined analyses [per standardized quintile increase in CRP, continuous OR = 0.94 (95% CI, 0.89-0.99), OR = 0.99 (95% CI, 0.95-1.04), OR = 0.98 (95% CI, 0.95-1.01), respectively]. In combined analyses, we observed a significant interaction (P(interaction) = 0.02) such that inverse associations were suggestive in younger (OR = 0.95; 95% CI, 0.90-1.01), but not older, participants.. Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer.. Our results highlight the importance of investigating more specific biomarkers for inflammation that may reflect the biological mechanisms underlying pancreatic cancer in prospective cohort studies.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; beta Carotene; C-Reactive Protein; Case-Control Studies; Cohort Studies; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Neoplasms; Placebos; Prognosis; Risk Assessment; Risk Factors; Vitamins

Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer.. We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided.. Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively).. Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer.

Topics: Aged; Alcohol Drinking; Antibodies, Bacterial; Anticarcinogenic Agents; beta Carotene; Coffee; Cohort Studies; Double-Blind Method; Energy Intake; Finland; Follow-Up Studies; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Reference Values; Risk Factors; Smoking; Time Factors; Vitamin E

Dietary components may be both causal and protective in cases of pancreatic carcinoma, but the preventive potential of single constituents has not been evaluated. The authors report the effects of alpha-tocopherol and beta-carotene supplementations on the rates of incidence of and mortality from pancreatic carcinoma in a randomized, controlled trial.. The 29,133 participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study were male smokers who were ages 50-69 years at the time they were randomized into 1 of the following 4 intervention groups: dl-alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both AT and BC, and placebo. The daily supplementation lasted for 5-8 years. Incident cancers were identified through the national Finnish Cancer Registry and death certificates of the Statistics Finland. Results were analyzed by supplementation with Cox regression models.. Effects of both supplementations were statistically nonsignificant. The rate of incidence of pancreatic carcinoma was 25% lower for the men who received beta-carotene supplements (n = 38) compared with the rate for those who did not receive beta-carotene (n = 51) (95% CI, -51% to 14%). Supplementation with alpha-tocopherol (n = 51) increased the rate of incidence by 34% (95% CI, -12% to 105%) compared with the rate for those who did not receive alpha-tocopherol. Mortality from pancreatic carcinoma during the follow-up, adjusted for stage and anatomic location of the tumor, was 19% (95% CI, -47% to 26%) lower among those who received beta-carotene and 11% (95% CI, -28% to 72%) higher among those who received alpha-tocopherol as compared with those who did not receive supplementation.. Supplementation with beta-carotene or alpha-tocopherol does not have a statistically significant effect on the rate of incidence of pancreatic carcinoma or the rate of mortality caused by this disease.

Topics: Aged; Antioxidants; beta Carotene; Carcinoma; Chemoprevention; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Pancreatic Neoplasms; Registries; Smoking; Vitamin E

Case-control studies of pancreatic cancer were conducted in 5 populations with moderate to high rates and differing dietary practices, using a common protocol and questionnaire. Comprehensive diet histories were completed for a total of 802 cases and 1669 controls identified in Adelaide (Australia), Montreal and Toronto (Canada), Utrecht (The Netherlands) and Opole (Poland). Positive associations were observed with intake of carbohydrates and cholesterol, and inverse associations with dietary fiber and vitamin C. These relationships were generally consistent among the 5 studies, and showed statistically significant and generally monotonic dose-response relationships. The relative risks for highest vs. lowest quintile of intake were estimated for carbohydrates to be 2.57 (95% confidence interval 1.64-4.03), cholesterol 2.68 (1.72-4.17), dietary fiber 0.45 (0.30-0.63), and vitamin C 0.53 (0.38-0.76). The consistency, strength, and specificity of these associations provides evidence for the hypothesis that some or all of these dietary factors may alter the risk of pancreatic cancer.

Topics: Adult; Aged; Ascorbic Acid; Australia; beta Carotene; Body Height; Body Weight; Canada; Carotenoids; Case-Control Studies; Cholesterol, Dietary; Diet; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Humans; Male; Middle Aged; Netherlands; Pancreatic Neoplasms; Poland; Vitamin A

Fucoxanthin and its metabolite fucoxanthinol (FxOH), highly polar xanthophylls, exert strong anticancer effects against many cancer cell types. However, the effects of Fx and FxOH on pancreatic cancer, a high mortality cancer, remain unclear. We herein investigated whether FxOH induces apoptosis in human pancreatic cancer cells. FxOH (5.0 μmol/L) significantly promoted the growth of human pancreatic cancer PANC-1 cells, but induced apoptosis in human colorectal cancer DLD-1 cells. A microarray-based gene analysis revealed that the gene sets of cell cycle, adhesion, PI3K/AKT, MAPK, NRF2, adipogenesis, TGF-β, STAT, and Wnt signals in PANC-1 cells were markedly altered by FxOH. A western blot analysis showed that FxOH up-regulated the expression of integrin β1 and PPARγ as well as the activation of pFAK(Tyr

Topics: Apoptosis; beta Carotene; Carotenoids; Cell Line, Tumor; Humans; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases

Pancreatic cancer is a devastating disease with poor prognosis. The association between vitamin A, retinol and carotenoid intake and the risk of pancreatic cancer occurrence remains controversial, and therefore it is necessary to make a meta-analysis to clarify the association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk. In the present study, PubMed and EMBASE databases were used to identify qualified studies. The association between dietary vitamin A, retinol and carotenoids was estimated by pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). It was found that there was an inverse correlation between vitamin A, beta-carotene and lycopene intake and the risk of pancreatic cancer (for vitamin A, pooled OR = 0.85, 95%CI = 0.74-0.97, P = 0.015; for beta-carotene, pooled OR = 0.78, 95%CI = 0.66-0.92, P = 0.003; for lycopene, pooled OR = 0.84, 95%CI = 0.73-0.97, P = 0.020), which was more prominent in case-control study subgroup. In conclusion, dietary vitamin A, beta-carotene and lycopene might inversely correlate with pancreatic cancer.

Topics: beta Carotene; Carotenoids; Female; Humans; Lycopene; Male; Pancreatic Neoplasms; Risk Factors; Vitamin A

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed.

Topics: alpha-Tocopherol; Analysis of Variance; beta Carotene; Blood Glucose; Cohort Studies; Computer Simulation; Dietary Supplements; Finland; Health Surveys; Humans; Incidence; Lung Neoplasms; Male; Monte Carlo Method; Pancreatic Neoplasms; Regression Analysis; Smoking; Survival Analysis

Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic cancer, are sources of oxidative stress in humans that could cause mitochondrial DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA copy number is associated with increased incident pancreatic cancer, we conducted a nested case-control study in the Alpha-Tocopherol Beta Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline. Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred (follow-up: 12 years) among participants, with whole blood samples used for mtDNA extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using unconditional logistic regression, adjusting for age, smoking, and diabetes history. All statistical tests were two sided. Higher mtDNA copy number was significantly associated with increased pancreatic cancer risk (highest vs. lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01-2.67, continuous OR = 1.14, 95% CI 1.06-1.23), particularly for cases diagnosed during the first 7 years of follow-up (OR = 2.14, 95% CI = 1.16-3.96, P(trend) = 0.01, continuous OR = 1.21, 95% CI = 1.10-1.33), but not for cases occurring during follow-up of 7 years or greater (OR = 1.14, 95% CI = 0.53-2.45, continuous OR = 1.05, 95% CI = 0.93-1.18). Our results support the hypothesis that mtDNA copy number is associated with pancreatic cancer and could possibly serve as a biomarker for pancreatic cancer development.

Topics: Adenocarcinoma; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Case-Control Studies; Diabetes Complications; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Double-Blind Method; Humans; Male; Middle Aged; Obesity; Pancreatic Neoplasms; Polymerase Chain Reaction; Prognosis; Risk Factors; Smoking

Topics: alpha-Tocopherol; beta Carotene; Case-Control Studies; Cohort Studies; Humans; Male; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Vitamin D

To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers.. The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.. The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.. Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.

Topics: Adult; Aged; beta Carotene; Colorectal Neoplasms; Esophageal Neoplasms; Factor V; Female; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Point Mutation; Retinoids; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

There have been few prospective studies relating diet to pancreatic cancer, with most having fewer than 100 cases and only one examining dietary nutrients. The authors prospectively examined dietary factors hypothesized to be associated with exocrine pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort in Finland. Of the 27,111 male smokers aged 50-69 years with complete dietary information, as ascertained from a self-administered dietary history questionnaire given at baseline (1985-1988), 163 developed pancreatic cancer from 1985 through November 1997. Cox proportional hazards models were used to estimate smoking- and age-adjusted hazard ratios and 95% confidence intervals. Energy-adjusted butter consumption and saturated fat intake were positively associated with pancreatic cancer (highest quintile vs. lowest: hazard ratio (HR) = 1.40, 95% confidence interval (CI): 0.87, 2.25 (p trend = 0.04), and HR = 1.60, 95% CI: 0.96, 2.64 (p trend = 0.02), respectively). Energy intake and energy-adjusted carbohydrate intake were inversely associated with the disease (highest quintile vs. lowest: HR = 0.62, 95% CI: 0.36, 1.07 (p trend = 0.05), and HR = 0.62, 95% CI: 0.37, 1.03 (p trend = 0.02), respectively). These results support the hypothesis that a high intake of saturated fat may increase the risk of pancreatic cancer in smokers, while greater intakes of energy and carbohydrate may reduce the risk.

Topics: Aged; alpha-Tocopherol; beta Carotene; Chi-Square Distribution; Diet; Dietary Carbohydrates; Dietary Fats; Energy Intake; Finland; Humans; Male; Middle Aged; Pancreatic Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Statistics, Nonparametric; Surveys and Questionnaires

The authors examined prospectively whether dietary folate and other factors known to influence methyl-group availability were associated with the development of exocrine pancreatic cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Of the 27,101 healthy male smokers aged 50--69 years who completed a self-administered dietary questionnaire at baseline, 157 developed pancreatic cancer during up to 13 years of follow-up from 1985 to 1997. Cox proportional hazards models were used to estimate the hazards ratios and 95% confidence intervals. The adjusted hazards ratio comparing the highest with the lowest quintile of dietary folate intake was 0.52 (95% confidence interval: 0.31, 0.87; p-trend = 0.05). Dietary methionine, alcohol intake, and smoking history did not modify this relation. No significant associations were observed between dietary methionine, vitamins B(6) and B(12), or alcohol intake and pancreatic cancer risk. Consistent with prior studies, this study shows that cigarette smoking was associated with an increased risk (highest compared with lowest quintile, cigarettes per day: hazards ratio = 1.82; 95% confidence interval: 1.10, 3.03; p-trend = 0.05). These results support the hypothesis that dietary folate intake is inversely associated with the risk of pancreatic cancer and confirm the risk associated with greater cigarette smoking.

Topics: Age Distribution; Aged; beta Carotene; Cohort Studies; Confidence Intervals; Diet; Finland; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Pancreatic Neoplasms; Probability; Proportional Hazards Models; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Survival Rate; United States; Vitamin E

The effects of alpha-carotene, beta-carotene, palm carotene, and green tea polyphenols (GTP) on the progression stage of pancreatic carcinogenesis after rapid production of ductal lesions were studied in Syrian hamsters. Dose threshold inhibitory effects were noted for beta-carotene, 25 ppm, and palm carotene, 40 ppm, which includes 24 ppm beta-carotene reducing the numbers of putative preneoplastic lesions of duct epithelial hyperplasia and atypical hyperplasia, as well as carcinoma in situ and invasive carcinomas. GTP at doses of 500 and 5000 ppm, but not 100 ppm, also significantly decreased the numbers of hyperplasia and total duct lesions. Combined administration of 40 ppm palm carotene, and 50 ppm GTP similarly inhibited the lesion development. Alpha-carotene, however, did not affect pancreatic carcinogenesis. The results suggest that chemopreventive effects are exerted by beta-carotene and GTP above critical doses and that combined administration of palm carotene and GTP might be a candidate chemoprevention strategy for pancreatic cancer in humans.

Topics: Animals; beta Carotene; Carcinogens; Carotenoids; Cricetinae; Female; Flavonoids; Fruit; Mesocricetus; Nitrosamines; Pancreas; Pancreatic Neoplasms; Phenols; Polymers; Polyphenols; Tea

The effects of vitamins E and E, beta-carotene and selenium on development of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumours in hamsters were investigated. Dietary supplementation of vitamin C, alone as well as in combination with beta-carotene resulted in consistently lower numbers of advanced ductular lesions. The differences with the controls, however, did not reach the level of statistical significance. Beta-Carotene alone demonstrated no inhibitory effect on the development of (pre)neoplastic lesions in the pancreas. Vitamin E or Se, either alone or in combination, had no effect on the development of advanced ductular lesions in BOP-treated hamsters.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; beta Carotene; Body Weight; Carcinogens; Carcinoma, Ductal, Breast; Carotenoids; Cricetinae; Diet; Male; Mesocricetus; Nitrosamines; Organ Size; Pancreatic Neoplasms; Selenium; Vitamin E

In the present study the effects of 0.1 or 1.0 g beta-carotene/kg diet (L beta C or H beta C) and 1.0 mg or 2.5 mg selenium/kg diet (LSel or HSel), as well as combinations of the respective low and high concentrations of beta-carotene and selenium (LMix or HMix) on the initiation/early promotion phase or on the late promotion phase of pancreatic carcinogenesis in azaserine-treated rats, were investigated using cell proliferation and volumetric data of atypical acinar cell foci (AACF) as parameters. The present results indicate chemopreventive effects of dietary selenium, dietary beta-carotene and of their combination on the development of acinar pancreatic lesions induced in rats by azaserine. The inhibitory effect was most pronounced when beta-carotene and/or selenium were added to the diets during the late promotion phase of the carcinogenic process, although inhibition was also observed with these compounds when they were added to the diets during the first 5 weeks of the study only (initiation/early promotion phase). Neither in the initiation/early promotion phase nor in the late promotion phase was a dose-related trend observed. The multiplicities of AACF with a diameter over 1.0 mm and of carcinomas in situ (CIS), as well as the incidence of CIS were not significantly different among the groups. However, in the late promotion experiment a dose-related decline in multiplicity could be observed in the selenium supplemented groups and in the groups receiving combinations of beta-carotene and selenium. Cell proliferation in azaserine-induced AACF, as estimated by the bromodeoxyuridine (BrdU) labeling index, was significantly higher in H beta C, HSel, LMix and HMix groups (initiation/early promotion phase) as well as in H beta C, LSel, HSel, LMix and HMix groups (late promotion phase) than in high fat controls. From the present results it can be concluded that: (i) beta-carotene and selenium have inhibitory effects on pancreatic carcinogenesis induced in rats by azaserine; (ii) the most clear effects were observed when selenium was given as such, or in combination with beta-carotene during the late promotion phase; and (iii) beta-carotene and selenium stimulate cell proliferation in AACF.

Topics: Analysis of Variance; Animals; Anticarcinogenic Agents; Azaserine; beta Carotene; Body Weight; Carcinogens; Carotenoids; Diet; Feeding Behavior; Female; Organ Size; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Wistar; Selenium

Risk factors for pancreatic cancer were examined in a cohort study of 13,979 residents of a retirement community. After 9 years of follow-up, 65 incident cases of pancreatic cancer were identified. An increased risk of pancreatic cancer was associated with a history of diabetes and cholecystectomy. Higher intake of vegetables, fruits, dietary beta-carotene, and vitamin C were each associated with a reduced risk of pancreatic cancer, although none of these associations was statistically significant. Risk of pancreatic cancer decreased with increasing tea consumption but was unrelated to coffee consumption. No strong or consistent association was seen between either smoking or alcohol consumption and risk of pancreatic cancer, but a consistent and significant increase in risk followed cholecystectomy.

Topics: Aged; Aged, 80 and over; Alcohol Drinking; Ascorbic Acid; beta Carotene; Carotenoids; Cholecystectomy; Coffee; Cohort Studies; Diabetes Mellitus; Diet; Female; Follow-Up Studies; Fruit; Humans; Incidence; Male; Pancreatic Neoplasms; Prospective Studies; Risk Factors; Smoking; Tea; Vegetables

A study was made on the effects of long-term dietary administration of beta-carotene, vitamin C, vitamin E and selenium, either alone or in combination, on azaserine-induced pancreatic carcinogenesis in rats. Male Wistar rats were given two i.p. injections of 30 mg azaserine per kg body weight at 19 and 26 days of age. The rats were allocated to eight groups of 40 animals each and were fed an AIN-76 diet rich in saturated fat (20% lard), either as such or after supplementation with beta-carotene, vitamin C, beta-carotene + vitamin C, vitamin E, selenium, vitamin E + selenium, or the combination of all micronutrients investigated. Fifteen months after the last treatment with azaserine the survivors were killed. The pancreata were examined for the number and size of advanced putative preneoplastic lesions and the number of neoplasms as well. Rats maintained on a diet high in either beta-carotene, vitamin C or selenium developed significantly less atypical acinar cells nodules, adenomas and carcinomas as compared to controls. The number of tumour-bearing animals was significantly lower in the groups fed the diet high in beta-carotene or selenium. In animals of the group given a diet high in all micronutrients investigated, both the number and incidence of pancreatic tumours was lower than in all other groups. It was concluded that selenium, beta-carotene and vitamin C, alone as well as in combination, have an inhibitory effect on pancreatic carcinogenesis induced in rats by azaserine.

Topics: Animals; Ascorbic Acid; Azaserine; beta Carotene; Body Weight; Carotenoids; Diet; Drug Combinations; Liver; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Regression Analysis; Selenium; Vitamin E

In a nested case-control study the stored, frozen sera from 22 cases of cancer of the pancreas and 44 matched control subjects were assayed for retinol, retinol-binding protein, total carotenoids, beta-carotene, lycopene, vitamin E (alpha-tocopherol), and selenium. Prediagnostic serum levels of lycopene and Se were lower among cases than among matched control subjects. These differences remained after adjustment was made for possible confounding by smoking, educational level, and the other measured serum levels. Low levels of serum vitamin E appeared to have a protective effect but a chance association between vitamin E and cancer of the pancreas could not reasonably be excluded. The association between cancer of the pancreas and serum Se was significant when the data were analyzed as a whole but its effect was seen principally in men.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Female; Humans; Lycopene; Male; Middle Aged; Pancreatic Neoplasms; Retinol-Binding Proteins; Risk Factors; Selenium; Smoking; Vitamin A; Vitamin E