beta-carotene and Urinary-Bladder-Neoplasms

Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary β-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 μmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 μmol/L increase in circulating concentration of β-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 μmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary β-cryptoxanthin intake and circulating concentrations of α-carotene, β-carotene, and lutein and zeaxanthin were inversely associated with BC risk. The protocol was registered at PROSPERO as CRD42019133240.

Topics: Adult; beta Carotene; Carotenoids; Female; Humans; Lutein; Male; Urinary Bladder Neoplasms; Zeaxanthins

This study aimed to investigate the effects of vitamin and antioxidant supplements in the prevention of bladder cancer using a meta-analysis of randomized controlled trials (RCTs). Fourteen RCTs were included in the final analysis. In a fixed-effect meta-analysis, vitamin and antioxidant supplements showed no preventive effect for bladder cancer (relative risk [RR] = 1.04; 95% confidence interval [CI] 0.92-1.17; I² = 39.7%). Also, there was no preventive effect of these supplements in the subgroup meta-analyses by various factors such as type of supplements, type of cancer prevention, methodological quality, providers of supplements, type of control group, and number of participants. Among the subgroup analyses by type of supplements, beta-carotene supplementation alone marginally increased the risk of bladder cancer (RR = 1.44; 95% CI 1.00-2.09; I² = 0.0%; n = 3). The current meta-analysis found that vitamin and antioxidant supplements have no preventive effect against bladder cancer.

Topics: Antioxidants; beta Carotene; Databases, Factual; Dietary Supplements; Humans; Randomized Controlled Trials as Topic; Risk; Urinary Bladder Neoplasms; Vitamins

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

In 1996, more than 300,000 new cases of bladder cancer were diagnosed worldwide. Besides tobacco smoking, occupation, and other factors, diet may play a role in causation of this illness. The authors performed a meta-analytical review of epidemiologic studies linking six dietary factors to bladder cancer. These factors include retinol, beta-carotene, fruits, vegetables, meat, and fat. Increased risks of bladder cancer were associated with diets low in fruit intake (relative risk (RR) = 1.40, 95% confidence interval (CI): 1.08, 1.83), and slightly increased risks were associated with diets low in vegetable intake (RR = 1.16, 95% CI: 1.01, 1.34). Elevated risks were identified for diets high in fat intake (RR = 1.37, 95% CI: 1.16, 1.62) but not for diets high in meat intake (RR = 1.08, 95% CI: 0.82, 1.42). No increased risks were found for diets low in retinol (RR = 1.01, 95% CI: 0.83, 1.23) or beta-carotene (RR = 1.10, 95% CI: 0.93, 1.30) intake. These results suggest that a diet high in fruits and vegetables and low in fat intake may help prevent bladder cancer, but the individual dietary constituents that reduce the risks remain unknown.

Topics: beta Carotene; Dietary Fats; Female; Fruit; Humans; Male; Meat; Risk; Urinary Bladder Neoplasms; Vegetables; Vitamin A

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Topics: beta Carotene; Clinical Trials as Topic; Dietary Fiber; Dietary Supplements; Epidemiologic Methods; Etretinate; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasms; Reproducibility of Results; Selenium; Urinary Bladder Neoplasms

Topics: Animals; Antineoplastic Agents; beta Carotene; Butylhydroxybutylnitrosamine; Carcinoma in Situ; Carcinoma, Papillary; Carotenoids; Cell Differentiation; Dose-Response Relationship, Drug; Epithelium; Fenretinide; Humans; Isotretinoin; Neoplasms; Neoplasms, Experimental; Tretinoin; Urinary Bladder Neoplasms; Vitamin A

There is little research investigating the role of vitamin D binding protein (DBP) in the association between 25-hydroxyvitamin D (25(OH)D) and disease risk.. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, 250 bladder cancer cases were randomly sampled and matched 1:1 to controls on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer were estimated by quartiles of DBP (measured by ELISA), 25(OH)D and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Analyses were also conducted stratifying 25(OH)D by DBP (median split) and vice versa.. We found no direct association between circulating DBP levels and bladder cancer risk (P-trend=0.83). The inverse association between 25(OH)D and bladder cancer risk was unchanged after adjustment for DBP (Q4 vs Q1 OR=0.61, 95% CI=0.36-1.05; P-trend=0.04), and was stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR=0.47, 95% CI=0.23-1.00; high DBP: 25(OH)D Q4 vs Q1 OR=0.83, 95% CI=0.40-1.75; P for interaction=0.11).. Our findings provide additional support for an aetiologic role for vitamin D in bladder cancer and suggest that free, rather than total, circulating vitamin D may be a more relevant exposure when examining bladder and, perhaps, other cancers.

Topics: alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Case-Control Studies; Double-Blind Method; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Urinary Bladder Neoplasms; Vitamin D; Vitamin D-Binding Protein

Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of α-tocopherol and β-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e., <25, 25 to <37.5, 37.5 to <50, ≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L; <25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to <37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to <50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend=0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend=0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women.

Topics: Aged; alpha-Tocopherol; beta Carotene; Case-Control Studies; Dietary Supplements; Double-Blind Method; Fasting; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Smoking; Urinary Bladder Neoplasms; Vitamin D

There is a growing body of basic science and epidemiologic evidence to support a research thrust to determine whether several natural or synthetic agents, given alone or together, can lower cancer incidence. Candidate agents include analogs of vitamin A and the vitamin A precursor, beta-carotene, vitamins C and E, and the trace metal selenium. Other agents now being studied in the laboratory include phenolic antioxidants, protease inhibitors, prostaglandin synthesis inhibitors, and indoles. Research in chemoprevention involves identifying and characterizing agents with reported activity, efficacy and toxicologic testing to select the most promising agents, and clinical trials to test those with the most potential in humans. Activities are underway in all the above areas, including 24 clinical trials, to evaluate selected compounds in preventing cancer at various cancer sites. Included are studies of individuals at high risk, individuals with precancerous lesions and individuals free of cancer but at risk to second cancers. A number of agents have shown activity in reducing bladder cancer incidence in animal models. The potential applicability of these agents for studies in human cancer risk reduction intervention studies is discussed. Cancer induction is postulated to be a multistage process involving initiation and promotion. Progress in cancer prevention may result from not only reducing exposures to initiators, but also suppressing promotional activity in initiated cells. Newly developed research technologies including cellular, animal, and epidemiologic procedures are being used for identifying, refining, and testing cancer prevention strategies.

Topics: Animals; Ascorbic Acid; beta Carotene; Carotenoids; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation; Epidemiologic Methods; Female; Humans; Male; Mice; Rats; Selenium; United States; Urinary Bladder Neoplasms; Vitamin A; Vitamin E

We evaluated the association of coffee and tea drinking with risk of the urinary tract cancer in Finnish men, with high coffee consumption, using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.. The ATBC trial conducted from 1985 to 1993 enrolled 29,133 male smokers. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and confidence intervals (CIs), using men who drank more than 0 but less than 1 cup coffee/d and tea nondrinkers as our referent group for coffee and tea analyses, respectively.. During 472,402 person-years of follow-up, 835 incident cases of bladder cancer and 366 cases of renal cell carcinoma were ascertained. For bladder cancer, we observed no association for coffee consumption (HR ≥4 vs. >0 to <1 cups/d = 1.16, 95% CI = 0.86-1.56) and a borderline statistically significant inverse association for tea consumption (HR ≥1 vs. 0 cup/d = 0.77, 95% CI = 0.58-1.00). For renal cell carcinoma, we observed no association for coffee (HR ≥4 vs. >0 to <1 cups/d = 0.85, 95% CI = 0.55-1.32) or tea consumption (HR ≥1 vs. 0 cup/d = 1.00, 95% CI = 0.68-1.46). We found no impact of coffee preparation on coffee-cancer associations.. Coffee drinking was not associated with urinary tract cancers risk. Further research on tea and bladder cancer is warranted.

Topics: Adult; Aged; alpha-Tocopherol; beta Carotene; Carcinoma, Renal Cell; Coffee; Cohort Studies; Female; Finland; Humans; Incidence; Male; Middle Aged; Prospective Studies; Risk Assessment; Tea; Urinary Bladder Neoplasms; Urologic Neoplasms

Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients, phytochemicals, and antioxidants with potentially anticarcinogenic properties. In a prospective analysis of 185,885 older adults participating in the Multiethnic Cohort Study, we examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk. Cox proportional hazards models were used to calculate HRs and 95% CIs for bladder cancer in relation to dietary intakes. A total of 581 invasive bladder cancer cases (429 men and 152 women) were diagnosed over a mean follow-up period of 12.5 y. In women, total fruits and vegetables [HR = 0.35 (95% CI: 0.22, 0.56); highest vs. lowest quartile], total vegetables [HR = 0.49 (95% CI: 0.29, 0.83)], yellow-orange vegetables [HR = 0.48 (95% CI: 0.30, 0.77)], total fruits [HR = 0.54 (95% CI: 0.34, 0.85)], and citrus fruits [HR = 0.56 (95% CI: 0.34, 0.90)] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids α-carotene, β-carotene, and β-cryptoxanthin; and folate had a lower risk of bladder cancer. For men, no associations for fruits, vegetables, or nutrients were found overall, although inverse associations were observed for vegetable intake among current smokers, and in ethnic-specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Cohort Studies; Cryptoxanthins; Ethnicity; Feeding Behavior; Female; Folic Acid; Follow-Up Studies; Fruit; Humans; Male; Middle Aged; Nutrition Assessment; Proportional Hazards Models; Prospective Studies; Risk Factors; Surveys and Questionnaires; Urinary Bladder Neoplasms; Vegetables; Vitamin E; Xanthophylls

A range of plausible biological mechanisms support preventive effects of micronutrients in bladder cancer. So far, however, results from the few epidemiological studies on the relation have been inconsistent, with no clear associations found.. To evaluate the association between total, dietary, and supplemental intake of beta-carotene, folate, vitamins C and E, and risk of urothelial carcinoma (UC) and to explore whether the association differs with smoking status.. The association was evaluated in the Danish Diet, Cancer and Health Study, comprising 55,557 men and women aged 50-64 yr at inclusion with no previous cancer diagnosis.. At baseline, all participants completed a detailed food frequency questionnaire including information on consumption of vitamin C, E, folate, and beta-carotene from diet and supplements. Incidence rate ratios (IRRs) of UC were calculated using Cox proportional hazards models.. During a median of 10.6 yr of follow-up, 322 UC cases were diagnosed. Vitamin C, E, and folate showed no association with UC, regardless of source. There was a significantly lower risk of disease with dietary beta-carotene consumption (IRR: 0.82; 95% confidence interval [CI]: 0.69-0.98) and a borderline significant lower risk with total beta-carotene intake (IRR: 0.85; 95% CI: 0.73-1.00) pr. 5000 μg of intake. We found a significant interaction between both dietary (p=0.005) and total (p=0.002) beta-carotene and smoking status, with a significant protective effect of beta-carotene seen among current smokers only.. Our results indicate no preventive effect of vitamin C, E, or folate on UC. We found a protective effect of dietary, but not supplemental, beta-carotene on UC, but further studies are required.

Topics: Ascorbic Acid; beta Carotene; Carcinoma, Transitional Cell; Denmark; Diet; Diet Records; Female; Folic Acid; Humans; Incidence; Male; Micronutrients; Middle Aged; Nutritional Status; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Smoking; Time Factors; Urinary Bladder Neoplasms; Urothelium; Vitamin E

Apart from smoking, certain occupational exposures, and schistosomiasis, little is known about other potential lifestyle risk factors for bladder cancer. Other investigations thus far have also been important because of the large number of individuals who are diagnosed with this cancer that apparently have no known risk factors. Preventing the recurrence of bladder cancer has generated some interest because several preliminary trials have found that a combination dietary supplement of vitamins and minerals or a probiotic agent (Lactobacillus casei) may impact this outcome favorably. Advising patients on some of these lifestyle modifications is currently recommended because the majority of them are also currently recommended for cardiovascular disease reduction.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arsenic; beta Carotene; Diet; Dietary Supplements; Exercise; Female; Humans; Life Style; Male; Neoplasm Recurrence, Local; Risk Factors; Smoking; Urinary Bladder Neoplasms; Vitamins

The association between several cancers and selenium status has been investigated in epidemiological studies. However, few results concerning bladder cancer have been reported thus far. The association between toenail selenium status and subsequent bladder cancer incidence was investigated in a prospective cohort study among 120,852 men and women aged 55-69 years at baseline (September 1986). The cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. Follow-up for incident cancer was established by record linkage to cancer registries until December 1992. The multivariable case-cohort analysis was based on 431 bladder cancer cases and 2,459 subcohort members, for whom toenail selenium levels were available. The age-, sex- and smoking-adjusted rate ratios (95% confidence intervals) for increasing quintiles of toenail selenium were 1.00 (reference), 1.09 (0.80-1.48), 0.55 (0.38-0.79), 0.63 (0.43-0.91), and 0.67 (0.46-0.97), respectively (P-trend < 0.01). Analyses with selenium as a continuous variable supported these findings. An inverse association between toenail selenium and bladder cancer risk was most pronounced among ex-smokers (P-trend < 0.01); was similar for subjects with high versus low intakes of beta-carotene, vitamin C, and vitamin E; and was mainly confined to invasive transitional cell carcinomas of the urinary bladder, irrespective of tumor morphology. We conclude that the evidence is in favor of an inverse association between selenium and bladder cancer risk.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Transitional Cell; Cohort Studies; Eating; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Statistics as Topic; Urinary Bladder Neoplasms; Vitamin E

The effects of the non-steroidal anti-inflammatory drug (NSAID) piroxicam and the carotenoids lycopene and beta-carotene, alone or in combination, on the development of rat superficial urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old, were given 0.05% BBN in the drinking water for 8 weeks followed by administration of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water) and/or beta-carotene (0.0025% in the drinking water) for 12 weeks, then killed for histological analysis of urinary bladder lesions. Cell proliferation potential was analyzed by immunohistochemical staining of the proliferative cell nuclear antigen (PCNA). Piroxicam alone, piroxicam+lycopene, and piroxicam +lycopene+ beta-carotene all significantly decreased the incidences and numbers of transitional cell carcinomas (TCCs), but the combination of piroxicam with carotenoids did not result in a clear improvement in the preventive potential of piroxicam. Piroxicam+ beta-carotene also caused a significant reduction and lycopene alone a slight but not significant reduction in the number of TCCs. In contrast, beta-carotene alone and lycopene+ beta-carotene were without inhibitory influence on any of the lesion categories examined, and the latter significantly increased the proportion of high-grade TCCs. Nevertheless, all of the chemopreventive agents, either alone or in combination, significantly decreased the TCC PCNA index, the effect extending to the surrounding epithelium in the piroxicam+lycopene and piroxicam+lycopene+beta-carotene groups. These results indicate that the NSAID piroxicam may be a more effective chemopreventive agent than lycopene and beta-carotene for superficial urinary bladder carcinogenesis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; beta Carotene; Butylhydroxybutylnitrosamine; Carcinogens; Carotenoids; Drug Interactions; Lycopene; Male; Piroxicam; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Urinary Bladder; Urinary Bladder Neoplasms

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week interval with tap water, water containing AX or CX at a concentration of 50 p.p.m. was administered during subsequent 20 weeks. Other groups of mice were treated with AX or CX alone or untreated. At the end of the study (week 41), the incidences of preneoplastic lesions and neoplasms in the bladder of mice treated with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In particular, AX administration after OH-BBN exposure significantly reduced the incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However, the inhibition of the frequencies of such lesions in mice treated with OH-BBN and CX was not significant. Treatment with AX or CX also decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), a new index of cell proliferation, in the transitional epithelium exposed to OH-BBN. Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative potential, was greater for AX than CX. These results indicate that AX is a possible chemopreventive agent for bladder carcinogenesis and such an effect of AX may be partly due to suppression of cell proliferation.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Body Weight; Butylhydroxybutylnitrosamine; Canthaxanthin; Carotenoids; Liver; Male; Mice; Mice, Inbred ICR; Nucleolus Organizer Region; Organ Size; Precancerous Conditions; Silver Staining; Urinary Bladder Neoplasms; Xanthophylls

To examine the association between serum nutrients and the development of bladder cancer we measured selenium, alpha-tocopherol, lycopene, beta-carotene, retinol, and retinol-binding protein in serum collected from 25,802 persons in Washington County, MD, in 1974. Serum samples were kept frozen at -70 degrees C. In the subsequent 12-year period, 35 cases of bladder cancer developed among participants. Comparisons of serum levels in 1974 among cases and two matched controls for each case showed that selenium was significantly lower among cases than controls (P = 0.03), lycopene was lower among cases at a borderline level of significance (P = 0.07), and alpha-tocopherol was nonsignificantly lower (P = 0.13). For selenium there was a nearly linear increase in risk with decreasing serum levels (P = 0.03). When examined by tertiles, the odds ratio associated with the lowest tertile of selenium compared to the highest tertile was 2.06. Serum levels of retinol, retinol-binding protein, and beta-carotene were similar among cases and controls. These results support a role for selenium in the prevention of bladder cancer.

Topics: Adult; Age Factors; Aged; beta Carotene; Biomarkers, Tumor; Carotenoids; Case-Control Studies; Female; Humans; Lycopene; Male; Middle Aged; Retinol-Binding Proteins; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Urinary Bladder Neoplasms; Vitamin A; Vitamin E

Inhibitors of human interferon action that might be relevant to tumour resistance or escape mechanisms were investigated in a macrophage system. The effects of IFN on macrophage Fc gamma receptor expression were inhibited by three preparations: (1) a low-molecular-weight component of normal autologous serum; (2) a low-molecular-weight component of carcinoma supernatant; and (3) physiological concentrations of retinol and retinoic acid. Since human carcinoma tissue contains abnormally high levels of retinoic acid-binding protein, the possibility that a tumour-associated retinoid contributes to tumour-induced inhibition in vitro was investigated. Inhibition of IFN action in vitro by retinoic acid (vitamin A acid) was found to be reversed by beta-carotene (pro-vitamin A). When tested in the tumour system beta-carotene also reversed inhibition by the human-carcinoma-derived signal. These data are consistent with the view that at least one of the tumour-derived signals inhibitory towards IFN is a tumour-associated retinoid, although firm evidence for this must await further physicochemical characterization of the inhibitory signal(s). The present data clearly show, nevertheless, that human tumour-induced inhibition of IFN in vitro can be reversed by the pro-vitamin beta-carotene.

Topics: beta Carotene; Carotenoids; Humans; Interferon Type I; Macrophages; Receptors, Fc; Urinary Bladder Neoplasms