Soy as Prostate Cancer Protection Yields Paradoxical Results

TOKYO, March 16 -- Diets rich in soy protect against prostate cancer. Then again, they don't.

This paradoxical finding came from a study of 43,509 Japanese men. For some soy isoflavones in the diet decreased the risk of localized prostate cancer, but at the same time soy containing miso soup increased the risk of advanced prostate cancer.

So reported Norie Kurahashi, M.D., of the National Cancer Center of Japan, and colleagues, in the March issue of Cancer Epidemiology, Biomarkers & Prevention.

"The present findings provide no clear understanding of when or how localized cancer will develop to aggressive cancer, and of the related effect of isoflavones," said Dr. Kurahashi.

The investigators recommended that Japanese men continue their high consumption of soy from foods, but they discouraged the use of supplements.

The investigators hypothesized that soy in general, and its isoflavones genistein and daizden in particular, may attenuate but not prevent the progression of latent prostate cancer. Soy isoflavones are estrogen mimics and strong antioxidants in vitro, and appear to be protective against cancer in animal models.

The Japanese study, the largest of its kind, prospectively evaluated the relationship between soy consumption and prostate cancer in men who were part of an even larger cohort study.

The men, ages 45 to 74 years, responded to a validated questionnaire which included 147 food and beverage items, including questions about portion size and frequency of consumption.

The authors focused on the consumption of miso, a soy-based soup, and at tofu in various forms, as well as natto, or fermented soybean, and soy milk. They also looked at the consumption of the isoflavones, which they estimated based on food composition tables listing isoflavone content of Japanese foods.

The study used as its baseline the five-year follow-up interval from the Japan Public Health Center-Based Prospective Study. Beginning in 1995 and continuing through 2004, there were 307 new cases of prostate cancer: 74 advanced, 220 organ-localized, and 13 of indeterminate stage.

The authors found that intake of genistein, daidzein, miso or soy foods did not have a significant effect on the risk of developing total prostate cancer (localized and advanced) for the entire cohort.

But when they broke the data down according to cancer by stage and age they found that men older than 60 in the highest quartile of intake of three of the four items -- genistein, daidzein, and soy foods -- had significantly decreased risk for localized prostate cancer versus those in the lowest quartile.

Of the men older than 60 with localized cancer, genistein was associated with a relative risk for cancer of 0.52 (95% CI, 0.30-0.90, P for trend = 0.03) in 25,538 person-years of follow-up.

Similarly, highest consumption of daidzein was associated with a relative risk of 0.50 (95% CI, 0.28-0.88, P for trend = 0.04) in 25,276 person-years, and soy foods were associated a relative risk of 0.52 (95% CI, 0.29-0.90, P for trend = 0.01).

There were no significant differences between the highest and lowest quartiles for any of the four items among men younger than 60, however.

When the investigators looked at advanced cancer among men older than 60 in a multivariate analysis adjusted for energy intake, there was a dose-dependent increase in risk for advanced prostate cancer associated with miso soup. There was a multivariable relative risk for the highest versus lowest quartile of 2.79 (95% CI, 1.19-6.55; P for trend = 0.02). Consumption of soy foods or the isoflavones was not associated with advanced prostate cancer in multivariate analysis, however.

"In the present study, we observed a dose-dependent decrease in the risk of localized prostate cancer with isoflavone consumption," the investigators wrote. "Men with the highest intake of isoflavones (as genistein, > 32.8 mg/d) had a decreased risk of prostate cancer compared with those with the lowest intake of isoflavones (as genistein, <13.2mg/d). To our knowledge, this is the first prospective study to report an inverse association between isoflavone and localized prostate cancer in Japanese, whose intake of soy food is high."

The reasons for their paradoxical findings of the effects of soy consumption by disease stage are unclear, but could be related to errors in food measurement, the small sample size of men with advanced prostate cancer (74 out of 307 total cases in a cohort of 43,509 men), or to a differential effect of related to the loss of estrogen receptors in advanced tumors, the authors suggested.

"A broad body of research is required to clarify the timing and period of isoflavones' preventive effect on prostate cancer development," Dr. Kurahashi said.

He and colleagues added, "Consumption of isoflavones from traditional Japanese food throughout life may protect against the incidence of prostate cancer, but we cannot recommend the use of isoflavones from supplements for people who do not regularly consume these chemicals, because the relationship between isoflavones and the risk of advanced prostate cancer is not yet clear."

Among the studies limitations were an inability to differentiate total prostate cancer cases from those detected through screening (which could have biased the sample toward health-conscious men who may eat more soy), the small number of advanced cancer cases, and possible misclassification of soy and isoflavone exposures because of changes in dietary consumption.