BLADDER CANCER  
 
 
 

#91 Review

Block G, Patterson B, Subar A

Dept. of Social and Administrative Health Sciences, School of Public Health, University of California, Berkeley 94720.

Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence.

Nutr Cancer 1992;18(1):1-29

Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods.  
 

#92 Book

World Cancer Research Fund/American Institute for Cancer Research

Food Nutrition and Prevention of Cancer: a global perspective.

American Institute for Cancer Research, Washington DC, 1997.

No Abstract. 
 

#149

Helzlsouer KJ, Comstock GW, Morris JS

Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.

Selenium, lycopene, alpha-tocopherol, beta-carotene, retinol, and subsequent bladder cancer.

Cancer Res 1989 Nov 1;49(21):6144-6148

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. 
 

#150

Okajima E, Ozono S, Endo T, Majima T, Tsutsumi M, Fukuda T, Akai H, Denda A, Hirao Y, Okajima E, Nishino H, Nir Z, Konishi Y

Department of Oncological Pathology, Nara Medical University, Kashihara.

Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and beta-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment.

Jpn J Cancer Res 1997 Jun;88(6):543-552

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. 
 

#171

Okajima E, Tsutsumi M, Ozono S, Akai H, Denda A, Nishino H, Oshima S, Sakamoto H, Konishi Y

Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara.

Inhibitory effect of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation.

Jpn J Cancer Res 1998 Jan;89(1):22-26

The effects of tomato juice on urinary bladder carcinogenesis were studied in male Fischer 344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. The animals (6 weeks old) were given 0.05% BBN in their drinking water for 8 weeks, followed by diluted tomato juice for 12 weeks, and killed at 20 weeks after the beginning of the experiment. Lycopene concentrations in the livers of rats given tomato juice were elevated. Histopathological analysis of urinary bladder lesions revealed the numbers, but not incidences, of urinary bladder transitional cell carcinomas (TCCs) to be decreased in the group given tomato juice. No influence on the incidence of simple and nodullopapillary hyperplasias, invasion or differentiation of TCC was noted. These results indicate that tomato juice, presumably the contained lycopene and other anti-oxidants in combination, exerts an inhibitory effect on the development of TCCs in the rat urinary bladder.  
 
 

#353

Garcia R, Gonzalez CA, Agudo A, Riboli E

Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.

High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer.

Nutr Cancer 1999;35(2):212-4

An analysis of a previously completed Spanish multicentric case-control study of bladder cancer was carried out using new available data on the contents in foods of specific carotenoids (alpha-carotene, beta-carotene, lutein, and lycopene) and flavonoids (quercetin, kaempferol, myricetin, and luteolin) to investigate the relationship of these phytochemicals with bladder cancer. The study included 497 cases first diagnosed with bladder cancer, 547 neighborhood controls, and 566 hospitals controls, matched by gender, age, area of residence, and hospital. Usual food intake was estimated using a dietary history questionnaire administered by trained interviewers. None of the specific carotenoids and none of the specific flavonoids have been found to be significantly associated with bladder cancer risk in this analysis. The adjusted odds ratios for subjects in the highest quartile of intake with respect to subjects in the lowest quartile were 1.36 (95% confidence interval = 0.94-1.95) for total carotenoid intake and 1.23 (95% confidence interval = 0.85-1.79) for total flavonoid intake. The results of this study does not support the hypothesis that intake of specific carotenoids and flavonoids is protective against bladder cancer risk. 
 
 

#536

Zhang, Zuo-Feng;  Lu, Qing-Yi;  Hung, Jui-Chun;  Heber, David

University of California, Los Angeles, CA, USA

Protective effects of plasma carotenoids on the risk of bladder cancer.

FASEB Journal VOL 15 NO 4 March 7, 2001

March 31-April 04, 2001

Annual Meeting of the Federation of American Societies for Experimental Biology on Experimental Biology 2001

Epidemiological studies have shown an inverse relationship between vegetables and fruit on the risk of bladder cancer by using food-frequency questionnaire. However, few studies have focused on the relationship between plasma levels of micro-nutrients and the risk of the disease. We conducted a case-control study with 84 cases and 173 controls at Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Blood samples were collected. Serum micronutrients including retinol, cryptoxanthin, lutein, zeaxanthin, lycopene, alpha-carotene and beta-carotene,gamma-tocopherol and alpha-tocopherol, were measured by high-performance liquid chromatography (HPLC). Logistic regression was applied to estimate the effects of micronutrients and to assess potential interactions between those micronutrients and cigarette smoking. Micronutrients were treated as both quartile and continues variables and other potential confounders, including age, sex, race, education, and pack-years of smoking were adjusted for in the model. Our results showed inverse dose-response relationships of following micronutrients. The ORs of alpha-carotene for the second, third, and the fourth quartiles were 0.494, 0.298, 0.122, respectively when the   lowest quartile was employed as baseline (trend p-value = 0.0321).  Consistently, the continuous logistic model also shows an inverse effects  of alpha-carotene (OR=3D0.223 p=3D0.0378). The strong protective effects of lutein, alpha-carotene, lycopene, zeaxanthin and cryptoxanthin on bladder cancer were also observed. The interactions of those micronutrient with cigarette smoking were also explored. Our results showed protective effects of the crotrenoids and suggested that bladder cancer is a preventable disease through nutritional intervention.  
 
 

#616

Zeegers MP, Goldbohm RA, Brandt PA.

Department of Epidemiology, Maastricht University, Maastricht

Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study.

Br J Cancer  2001 Sep;85(7):977-83

In the Netherlands Cohort Study among 120 852 subjects aged 55-69 years at baseline (1986), the association between vitamins and carotenoids intake, vitamin supplement use, and bladder cancer incidence was examined. Exposure status was measured with a food-frequency questionnaire. After 6.3 years of follow-up, data from 569 cases and 3123 subcohort members were available for case-cohort analyses. The age-, sex-, and smoking-adjusted relative risks (RRs) for retinol, vitamin E, folate, a-carotene, b-carotene, lutein and zeaxanthin, and lycopene were 1.04, 0.98, 1.03, 0.99, 1.16, 1.11, and 1.08, respectively, comparing highest to lowest quintile of intake. Only vitamin C (RR: 0.81, 95% CI: 0.61-1.07, P-trend = 0.08), and b-cryptoxanthin intake (RR: 0.74, 95% CI: 0.53-1.03, P-trend < 0.01) were inversely associated with bladder cancer risk. The association with vitamin C disappeared after adjustment for b-cryptoxanthin

but not vice versa. The RRs for supplemental use of vitamin A, C or E compared to no use were around unity. We conclude that dietary or supplemental intake of vitamin A, vitamin C, vitamin E, and intake of folate, and most carotenoids are not associated with bladder cancer. In this study, only b-cryptoxanthin intake appeared to be inversely associated.  
 

#745

Michaud DS, Pietinen P, Taylor PR, Virtanen M, Virtamo J, Albanes D.

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics,

National Cancer Institute, Rockville, MD 20852, USA. michaudd@mail.nih.gov

Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study.

Br J Cancer  2002 Oct 21;87(9):960-5

We examined the relation between dietary fruit and vegetables, carotenoids and

vitamin intakes and the risk of bladder cancer among male smokers in a

prospective cohort study. Over a median of 11 years, we followed 27 111 male

smokers aged 50-69 years who were initially enrolled in the Alpha-Tocopherol

Beta-Carotene Cancer Prevention Study. During this period, 344 men developed

bladder cancer. All of these men had completed a 276-food item dietary

questionnaire at baseline. Cox proportional hazards models were used to estimate

the relative risks and 95% confidence intervals and to simultaneously adjust for

age, smoking history, energy intake and intervention group. Consumption of

fruits and vegetables was not associated with the risk of bladder cancer

(relative risk=1.28; 95% confidence intervals CI: 0.89-1.84, for highest vs

lowest quintile). Similarly, no associations were observed for groups of fruits

or vegetables (berries and cruciferous vegetables), or for specific fruits and

vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene,

lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not

related to the risk of bladder cancer. These findings suggest that fruit and

vegetable intakes are not likely to be associated with bladder cancer risk.

However, these results may not be generalisable to non-smokers.