Fruit and Vegetable Consumption and Risk of Bladder Cancer: A Prospective Cohort Study

Bladder cancer incidence and mortality rates vary substantially across geographic regions (1), suggesting that environmental factors, such as diet, may play a role in the etiology of this malignancy. With regard to dietary factors, a high consumption of fruits or vegetables has been associated with a decreased risk of bladder in the majority of case-control studies (2-9). However, the retrospective design of these studies may have introduced recall and selection biases. Prospective cohort studies of fruit and vegetable consumption in relation to bladder cancer risk are inconclusive, with an inverse association observed for intake of fruits (10-14) and/or vegetables (12, 15) in some studies but not in others (16-18). Given the inconsistent results, we used data from the Swedish Mammography Cohort and the Cohort of Swedish Men to assess prospectively the relationship between fruit and vegetable intake and bladder cancer incidence.

The Swedish Mammography Cohort was established between 1987 and 1990, when all women born between 1914 and 1948 and residing in central Sweden received a mailed questionnaire on diet, body size, and education. In the autumn of 1997, all surviving participants received a new expanded questionnaire that included about 350 items concerning diet and other lifestyle factors; 39,227 women answered the questionnaire. For the current analyses, eligible women were those who completed the 1997 questionnaire because information on smoking (a strong risk factor for bladder cancer) was not available in the baseline questionnaire. The Cohort of Swedish Men began in the autumn of 1997, when all men born between 1918 and 1952 and residing in central Sweden received a questionnaire that was identical (except for some sex-specific questions) to the 1997 Swedish Mammography Cohort questionnaire; 48,850 men returned a completed questionnaire. After exclusion of participants with an erroneous or missing National Registration Number, those with implausible values for total energy intake (3 SDs from the log_e-transformed mean energy intake), and those with a previous cancer diagnosis (other than nonmelanoma skin cancer), 82,002 participants (36,664 women and 45,338 men) remained for analyses.

A self-administered 96-item food frequency questionnaire was used to assess usual dietary intake over the previous year. In our validation study, the Spearman correlation coefficients between the average of four 1-week diet records and the dietary questionnaire ranged from 0.4 to 0.7 for individual fruit and vegetable items.³

Cases of bladder cancer were identified by linking cohort participants to the National Swedish Cancer Register and the Regional Cancer Register covering the study area. The completeness of cancer follow-up was estimated to be almost 100% (19). The endpoint for the present analyses was incident bladder cancer coded according to the International Classification of Disease for Oncology, Second Revision (codes C67.0-C67.9), excluding in situ bladder cancer (n = 20). Information on dates of death for deceased participants was obtained from the Swedish Death Registry.

Participants contributed person-time from baseline to the date of diagnosis of bladder cancer, death, or December 31, 2007, whichever came first. Quartiles of fruit and vegetable intake were derived based on the distribution in the total study population. We used Cox proportional hazards models (20) to estimate rate ratios (RR) and 95% confidence intervals (95% CI) adjusted for age and sex. Multivariate models were further adjusted for education and cigarette smoking. Tests for trend were conducted using the median value for each quartile as a continuous variable. All P values were two sided. The study had 80% power to detect a RR < 0.67 for the highest versus lowest quartile (α = 0.05, two sided).

During a mean follow-up of 9.4 years (772,272 person-years), 485 incident bladder cancer cases (76 women and 409 men) were ascertained. Women and men with a high intake of fruits and vegetables were more likely to have a postsecondary education and to be never smokers compared with those with a low fruit and vegetable intake (Table 1).

Total fruit and vegetable intake was inversely associated with bladder cancer risk when adjusting for age and sex only (Table 2). However, the association was attenuated and not statistically significant after further adjustment for education and smoking. Intakes of total fruits, citrus fruits, total vegetables, cruciferous vegetables, or green leafy vegetables were not associated with risk of bladder cancer. Exclusion of cases diagnosed during the first 2 years of follow-up did not change the results appreciably. We found no evidence that the association between fruit and vegetable intake and bladder cancer risk was modified by sex (P_interaction = 0.24) or smoking status (P_interaction = 0.55). The multivariate RRs (95% CIs) of bladder cancer comparing the highest with the lowest quartile of total fruit and vegetable intake were 0.79 (0.44-1.43) in never smokers, 0.78 (0.50-1.23) in past smokers, and 0.75 (0.47-1.21) in current smokers.

To examine more extreme intakes of fruits and vegetables, we categorized participants into deciles of total fruit and vegetable intake. Participants in the highest decile of fruit and vegetable intake (≥7.9 servings/d; n = 26 cases) had a nonsignificant lower risk of bladder cancer (multivariate RR, 0.64; 95% CI, 0.40-1.03) compared with those in the lowest decile (<1.7 servings/d; n = 77 cases). The multivariate RR (95% CI) of bladder cancer for a 5 servings/d increment of fruit and vegetable intake was 0.86 (0.69-1.07; P_trend = 0.19).

In this large prospective cohort study, intakes of fruits and vegetables were not significantly associated with bladder cancer risk after adjustment for potential confounders. This study has several strengths including a large sample size, the population-based and prospective design, detailed information on diet and smoking status and history, and the completeness of case ascertainment through linkage to Swedish cancer registries. The prospective nature of our study avoided recall and selection biases, which could be a problem in case-control studies. We cannot exclude measurement error due to self-reported diet as a contributor to the lack of association with fruit and vegetables intake in the present study. Nevertheless, we have observed an inverse association between vegetable intake and gastric cancer risk in this study population (21), suggesting that failure to observe a protective association with bladder cancer was unlikely due to an inability to assess fruit and vegetable intake.

In conclusion, we found no evidence that higher intakes of fruits and vegetables during adulthood reduce the risk of bladder cancer.

No potential conflicts of interest were disclosed.

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