Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker.
Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker.
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DOI：
10.1158/1055-9965.epi-20-0133
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Tinker LF
中科院分区：
文献类型：
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作者：
Reding KW;Han CJ;Whittington D;Zahid M;Rogan EG;Langford D;Rohan TE;Chlebowski RT;Cheng TD;Barrington WE;Tinker LF
遗传毒性雌激素，即雌激素DNA加合物(EDA)，在乳腺癌的发生发展中起作用，这在生物学上是可信的。支持来自之前的三项研究，它们报告了乳腺癌患者相对于对照女性EDA浓度相对于雌激素代谢物和结合物(EDA：EMC)的浓度升高。在参与妇女健康倡议(WHI)的绝经后妇女中，191名对照的EDA：EMC与来自乳腺癌病例的194份诊断前尿样的结果进行了比较。EDA：EMC测定采用如前所述的质谱仪，并采用Logistic回归估计优势比(OR)。EDA：EMC在乳腺癌病例中与对照组总体(0.93[95%CI：0.71-1.23])相比没有差异，病例和对照组的平均(SD)分别为2.3(0.8)和2.4(1.1)。同样，当通过雌激素受体或乳腺癌前生物标本收集的近期情况进行检查时，这一比例没有差异。尽管某些儿茶酚雌激素的遗传毒性特性会导致雌激素DNA加合物，但这项分析并未提供与EDA：EMC升高有关的乳腺癌风险增加的证据。这项在WHI研究中对绝经后女性进行的前瞻性分析表明，可以排除EDA：EMC与乳腺癌之间的强烈关联，因为这项研究能够检测到OR为2.2或更高。
It is biologically plausible that genotoxic estrogens, namely estrogen DNA adducts (EDA), have a role in breast cancer development. Support comes from three prior studies which reported elevated concentrations of EDA relative to estrogen metabolites and conjugates (EDA:EMC) in women with breast cancer relative to control women. In postmenopausal women in the Women’s Health Initiative (WHI), EDA:EMC in 191 controls was compared to findings in 194 pre-diagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate the odds ratios (OR). The EDA:EMC did not differ in breast cancer cases compared to controls overall (0.93 [95% CI: 0.71–1.23]), with a mean (SD) of 2.3 (0.8) and 2.4 (1.1) in cases and controls, respectively. Similarly, the ratio did not differ when examined by estrogen receptor or recency of biospecimen collection prior to breast cancer. Despite the demonstrated genotoxic properties of certain catechol estrogens resulting in estrogen DNA adducts, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC. This analysis conducted prospectively within post-menopausal women in the WHI study suggests that a strong association between EDA:EMC with breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.