Soy Intake is Associated with Increased 2-Hydroxylation and Decreased 16α-Hydroxylation of Estrogens in Asian-American Women

Introduction: In Asian and Asian-American women, soy consumption is associated with reduced breast cancer risk, perhaps due to its effects on estrogen production or metabolism. In a sample of Asian-American women, we investigated the associations of usual adult soy intake with the urinary concentrations of 15 estrogens and estrogen metabolites (EM) measured using liquid chromatography-tandem mass spectrometry. Methods: Participants included 430 Chinese-American, Japanese-American, and Filipino-American women, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California), or Oahu (Hawaii). They were postmenopausal (n = 167) or premenopausal in luteal phase (n = 263) when 12-hour urine samples were collected. Robust linear regression was used to assess soy tertiles as predictors of log-transformed EM measures. Individual and grouped EM were considered as concentrations (pmol/mg creatinine) and as percentages of total EM (%EM). Results: Factor analysis confirmed that EM groups defined by metabolic pathways appropriately captured covariation in EM profiles. Total EM concentrations were not significantly associated with soy in premenopausal or postmenopausal women. Among all women, %2-hydroxylated EM and %4-hydroxylation pathway EM were 16% higher (Ptrend = 0.02) and 19% higher (Ptrend = 0.03) in the highest versus lowest soy tertiles, respectively. In contrast, 16% hydroxylated EM were 11% lower (Ptrend < 0.01). Results were consistent across ethnic and menopausal groups and after adjustment for westernization measured by birthplace (Asia or United States). Discussion: Findings suggest that regular soy intake is associated with increased ratios of 2:16-pathway EM and with higher relative levels of 4-hydroxylated EM. The observed variations in estrogen metabolism might modify breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2751–60)