University of Washington School of Nursing, Seattle, Washington.
Fred Hutch Cancer Research Center Public Health Sciences, Seattle, Washington.
Cancer Epidemiol Biomarkers Prev. 2020 Oct;29(10):2096-2099. doi: 10.1158/1055-9965.EPI-20-0133. Epub 2020 Jul 22.
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 that 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 with findings in 194 prediagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate ORs.
EDA:EMC did not differ in breast cancer cases compared with controls overall [0.93 (95% confidence interval, 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 EDAs, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC.
This analysis, conducted prospectively within postmenopausal women in the WHI study, suggests that a strong association between EDA:EMC and breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.
具有遗传毒性的雌激素，即雌激素 DNA 加合物（EDA），可能在乳腺癌的发展中起作用，这在生物学上是合理的。有三项先前的研究支持这一观点，这些研究报告称，与对照组女性相比，乳腺癌女性的 EDA 相对于雌激素代谢物和缀合物（EDA：EMC）的浓度升高。
在妇女健康倡议（WHI）中的绝经后妇女中，191 名对照者的 EDA：EMC 与 194 名乳腺癌病例发病前尿液样本中的发现进行了比较。EDA：EMC 的测定如前所述通过质谱法进行，采用逻辑回归估计 OR。
总体而言，乳腺癌病例与对照组的 EDA：EMC 没有差异[0.93（95%置信区间，0.71-1.23）]，病例和对照组的平均值（SD）分别为 2.3（0.8）和 2.4（1.1）。同样，当按雌激素受体或生物样本采集时间（发病前）进行检查时，该比值也没有差异。
尽管某些儿茶酚雌激素具有遗传毒性特性，导致 EDA，但这项分析并未提供证据表明 EDA：EMC 升高与乳腺癌风险增加有关。
这项在 WHI 研究中的绝经后妇女中进行的前瞻性分析表明， EDA：EMC 与乳腺癌之间的强烈关联可以排除，因为这项研究的目的是检测 OR 大于或等于 2.2。
