Dietary isoflavone intake and breast cancer risk in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians

B48

Background: Although epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk, little evidence for a dose-response relation is available. To evaluate the dose-response relationship between isoflavone intake and the risk of breast cancer, ranging from zero to a relatively high level achievable from dietary intake only, we conducted hospital-based case-control studies in Nagano, Japan and São Paulo, Brazil, targeting three populations: Japanese living in Japan, Japanese Brazilians living in São Paulo and non-Japanese Brazilians living in São Paulo.
 >Method: Cases were a consecutive series of female patients aged 20-74 years who were newly diagnosed with histologically confirmed invasive breast cancer. Age- and area- matched controls were selected from medical checkup examinees in Nagano, Japan, and age- and ethnic-matched controls were selected from cancer-free patients in São Paulo, Brazil. A total of 850 pairs (390 Japanese, 81 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and the odds ratio (OR) and 95% confidence interval (CI) of breast cancer according to isoflavone intake was estimated using a conditional logistic regression model.
 >Results: Isoflavone intake substantially varied among populations; mean genistein intake (mg/day) in control subjects were 28.6 for Japanese, 15.8 for Japanese Brazilians, and 3.1 for non-Japanese Brazilians. We found a statistically significant inverse association between genistein intake and the risk of breast cancer for Japanese Brazilians and non-Japanese Brazilians. Adjusted OR for the highest versus lowest tertile of genistein intake was 0.28 (95% CI 0.11-0.72; p for trend = <0.01) for Japanese Brazilians. For non-Japanese Brazilians, the adjusted OR for consumers versus non-consumers of genistein was 0.55 (95% CI 0.34-0.88). For Japanese, a statistically significant inverse association was limited to postmenopausal women (highest versus lowest tertile of genistein intake: adjusted OR = 0.58, 95% CI 0.36-0.95, p for trend = 0.03). In the three populations combined, the risk of breast cancer was linearly decreased from non-consumers to the third quintile group but leveled off from the third to the highest quintile group. Compare to subjects in the lowest quintile category, adjusted ORs were 1.50 (95% CI 0.95-2.38) for non-consumers and 0.57 (95% CI 0.35-0.92) for those in the highest quintile category. Moreover, we found no remarkable difference between genistein intake and the risk of hormone receptor-defined subtypes.
 >Conclusion: We found an inverse association between dietary genistein intake and the risk of breast cancer. Our finding of a dose-response relation suggests that women may benefit from risk reduction if they consume at least moderate amounts of isoflavones.