Journal
ENDOCRINE-RELATED CANCER
Volume 21, Issue 2, Pages 263-273Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-13-0233
Keywords
breast cancer; estrogen; estrogen receptor; estrogen receptor bioassay
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Funding
- Singapore Cancer Society Cancer Research Grant (DRA) [2010-09-083]
- Singapore National Medical Research Council [R-174-000-137-275]
- National Institutes of Health, USA [NCI RO1 CA55069, R35 CA53890, R01 CA80205, R01 CA144034]
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The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case-control study in 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort study, the Singapore Chinese Health Study, to evaluate the serum levels of estrogens and their receptor (ER alpha and ER beta)-mediated estrogenic activities in relation to breast cancer risk. Breast cancer cases had higher levels of estrogens and ER-mediated bioactivities in baseline serum than the controls. Compared with those in the lowest quartile, women in the highest quartile for estrone (E-1) or ER alpha-mediated bioactivity had increased breast cancer risk. After additional adjustment for ERb bioactivity, free estradiol, and E1 levels, serum ERa-mediated bioactivity remained associated with increased breast cancer risk. Compared with those in the lowest quartile, women in the highest quartile for ERa-mediated bioactivity had an odds ratio of 2.39 (95% CI=1.17-4.88; P for trend=0.016). Conversely, the positive association between E-1 and cancer risk became null after adjustment for ER alpha-mediated bioactivity, suggesting that the effect of E-1 could be mediated through ER alpha. Factor(s) contributing to increased ER alpha-mediated estrogenic bioactivity in serum and its role as a predictor for breast cancer risk need to be validated in future studies.
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