Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1674-7.
Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study.
Sun CL, Yuan JM, Arakawa K, Low SH, Lee HP, Yu MC.
USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
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The association between soyfood consumption and subsequent bladder cancer risk was investigated in a population-based cohort study, the Singapore Chinese Health Study. As of December 31, 2000, 329,848 person-years of follow-up were accrued. Sixty-one histologically confirmed incident bladder cancer cases were identified. Information on soyfood consumption at baseline was obtained through in-person interviews using a validated dietary questionnaire. Relative risks and 95% confidence intervals were calculated using the Cox proportional hazard regression method. High intake of soyfood was statistically significantly related to an elevated risk of bladder cancer. Relative to the lowest quartile of energy-adjusted total soy intake (<36.9 g/1000 Kcal), the highest quartile of total soy intake (> or =92.5 g/1000 Kcal) was associated with a 2.3-fold increase in bladder cancer risk (95% confidence interval = 1.1-5.1) after adjustment for cigarette smoking and level of education. Similar results were obtained for intakes of soy protein and soy isoflavones. The soyfood-bladder cancer risk association did not differ significantly between men and women and was not explained by other dietary factors. The soy-cancer relationship became stronger when the analysis was restricted to subjects with longer (> or =3 years) duration of follow-up. To our knowledge, this is the first epidemiological report on the effect of dietary soy on bladder cancer risk.

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To our knowledge, this study is the first epidemiological investigation on dietary soy and bladder cancer risk. The data from in vitro and whole animal studies have yielded conflicting results on the role of dietary soy in bladder carcinogenesis. Mokhtar et al. (4) reported that dietary soy reduced nitrosamine-induced bladder tumors in mice. Soy isoflavones or soy concentrate inhibited both growth of human bladder cancer cells in vitro and growth of implanted murine or human bladder cancer in nude mice (5). On the other hand, laboratory studies involving human bladder cancer cells (17) and whole animals (18) have supported a role of insulin-like growth factor-1 in bladder carcinogenesis, and a recent randomized, double-blind, placebo-controlled feeding experiment observed that men given soy protein supplements exhibited significant increase in serum insulin-like growth factor-1 level (19).

Results regarding the association between dietary soy and other cancers are equally conflicting. Soy was shown to inhibit growth of colon cancer cells (20) and the development of chemically induced colon cancer in rats (21). However, administration of genistein to male rats treated with a colon carcinogen led to enhanced colon cancer development (22). Available epidemiological data indicate that dietary soy has no effect on colon cancer risk (23). Additionally, genistein was shown to promote growth of human pancreatic tumor cells (24) and induce chromosomal aberrations in human peripheral blood lymphocytes (25).

It is possible that some unidentified substances in soyfoods are responsible for the observed adverse effect on the development of bladder cancer. In fact, our data showed a stronger positive association with total soy than with soy protein or soy isoflavones. It is also conceivable that soyfood is a surrogate of some other as-yet-unidentified constituents in the diet that relate to an increased risk of bladder cancer.

Since 1999, when the Food and Drug Administration concluded that soy protein included in a diet low in saturated fat and cholesterol may reduce the risk of coronary heart disease, there has been a noticeable increase in the consumption and production of soyfoods in the United States. According to national surveys conducted by the United Soybean Board, 27% of Americans reported using soy products at least once a week in the year 2000, up from 15% in the year 1998 (26). Therefore, the risk versus benefit of dietary soy in disease causation carries important public health implications.

Urine is an important route for the excretion of soy constituents such as genistein, daidzein, and their metabolites. In fact, the concentration of genistein in the urine is considerably higher than that in blood (27). Thus, a possible effect of dietary soy on bladder cancer risk warrants further study. We caution that our novel finding of a positive association between soy and bladder cancer risk is based on a relatively short period of follow-up and a modest number of cancer cases. If this provocative observation is confirmed by others, laboratory studies to delineate possible mechanisms will be needed.

Categories: 2002, Soy, Cancer, IGF-1, Nutrition and diet