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Background: The role of estrogen metabolism in determining breast cancer risk and differences in breast cancer rates between high-incidence and low-incidence nations is poorly understood.Methods: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 estrogen metabolites formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in a nested case-control study of 399 postmenopausal invasive breast cancer case participants and 399 matched control participants from the population-based Shanghai Women's Health Study cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by quartiles of metabolic pathway groups, pathway ratios, and individual estrogens/estrogen metabolites were estimated by multivariable conditional logistic regression. Urinary estrogen/estrogen metabolite measures were compared with those of postmenopausal non-hormone-using Asian Americans, a population with three-fold higher breast cancer incidence rates. All statistical tests were two-sided.Results: Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (ORQ4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, Ptrend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (ORQ4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, Ptrend = .03, and ORQ4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, Ptrend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (ORQ4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, Ptrend = .12 and ORQ4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, Ptrend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women.Conclusions: Lower urinary parent estrogen concentrations and more extensive 2-hydroxylation were each associated with reduced postmenopausal breast cancer risk in a low-risk nation. Markedly higher total estrogen/estrogen metabolite concentrations in postmenopausal United States women (Asian Americans) than in Shanghai women may partly explain higher breast cancer rates in the United States. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives The role of estrogens among men has rarely been explicitly considered. We examined differences in total, free, and bioavailable estradiol (Bio E) between young men from the United States (US) and the most economically developed part of China, that is, Hong Kong (HK). Methods Cross-sectional analysis was conducted based on 365 young men from the Third National Health and Nutrition Examination Survey in the US and 299 young Chinese men. All participants were aged from 18 to 29 years. Main outcome measures were total estradiol (E2) and calculated Bio E and free estradiol (FE). Results In both young US and Chinese men, E2 concentrations peaked at ages 25-29 years, at 43.3 pg/ml [95% confidence interval (CI) 41.9-44.8] in US men and 29.0 pg/ml (95% CI 26.2-32.0) in Chinese men. After adjustment for age and ethnicity, in all participants, US men had higher average concentrations of E2 [39.0 (95% CI 38.6-39.4) versus 28.3 (95% CI 28.3-28.4) pg/ml], FE [72.9 (95% CI 72.7-73.7) versus 56.8 (95% CI 56.6-56.9) ng/dl], and Bio E [17.9 (95% CI 17.7-18.1) versus 14.9 (95% CI 14.8-14.9) pg/ml] than HK men. Further adjustment for height or body mass index did not change the results. Conclusions Estradiol, and free and Bio E concentrations are much lower in young healthy Chinese men than US men. However, these findings based on comparison between the two assays in the two different locations need further confirmation. Am. J. Hum. Biol. 26:565-569, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer.Participants and methods: We compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women.Results: In both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (−36.8%).Conclusions: Taking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women. [ABSTRACT FROM PUBLISHER]