Endogenous Estrogens, Estrogen Metabolites, and Breast Cancer Risk in Postmenopausal Chinese Women

<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background:</strong> 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. <strong>Methods:</strong> 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. <strong>Results:</strong> Urinary concentrations of parent estrogens were strongly associated with breast cancer risk (OR _Q4vsQ1 = 1.94, 95% CI = 1.21 to 3.12, <span style="font-style:italic;">P</span>_trend = .01). Of the pathway ratios, the 2-pathway:total estrogens/estrogen metabolites and 2-pathway:parent estrogens were inversely associated with risk (OR _Q4vsQ1 = 0.57, 95% CI = 0.35 to 0.91, <span style="font-style:italic;">P</span>_trend = .03, and OR _Q4vsQ1 = 0.61, 95% CI = 0.37 to 0.99, <span style="font-style:italic;">P</span>_trend = .04, respectively). After adjusting for parent estrogens, these associations remained clearly inverse but lost statistical significance (OR _Q4vsQ1 = 0.65, 95% CI = 0.39 to 1.06, <span style="font-style:italic;">P</span>_trend = .12 and OR _Q4vsQ1 = 0.76, 95% CI = 0.44 to 1.32, <span style="font-style:italic;">P</span>_trend = .28). The urinary concentration of all estrogens/estrogen metabolites combined in Asian American women was triple that in Shanghai women. <strong>Conclusions:</strong> 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. </span>

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