Arslan Alan A, Koenig Karen L, Lenner Per, Afanasyeva Yelena, Shore Roy E, Chen Yu, Lundin Eva, Toniolo Paolo, Hallmans Göran, Zeleniuch-Jacquotte Anne
Authors' Affiliations: Departments of Obstetrics and Gynecology, Population Health, and Environmental Medicine, New York University School of Medicine; New York University Cancer Institute, New York, New York; Departments of.
Population Health, and Environmental Medicine, New York University School of Medicine;
Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1290-7. doi: 10.1158/1055-9965.EPI-14-0009. Epub 2014 Apr 27.
It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16α-hydroxylation pathway may be inversely associated with breast cancer risk.
We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and the 2-OHE1:16α-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16α-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation.
Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16α-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P ≤ 0.03). We observed a protective association of 2-OHE1 with ER+ breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)].
In this study, higher levels of 2-OHE1 were associated with reduced risk of ER+ breast cancer in postmenopausal women after adjustment for circulating estrone.
These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.
有假设认为，与16α-羟基化途径相比，2-羟基化雌激素代谢途径占主导地位可能与乳腺癌风险呈负相关。
在一项嵌套于两个前瞻性队列中的绝经后女性病例对照研究中，我们研究了浸润性乳腺癌风险与循环2-羟基雌酮（2-OHE1）、16α-羟基雌酮（16α-OHE1）以及2-OHE1:16α-OHE1比值之间的关联。这两个队列分别是纽约大学女性健康研究（NYUWHS）和瑞典北部乳腺筛查队列（NSMSC），并对雌酮的循环水平进行了校正，同时按肿瘤雌激素受体（ER）状态进行了额外分析。采用ESTRAMET 2/16分析法测定了499例新发乳腺癌病例和499例对照的储存血清或血浆样本中2-OHE1和16α-OHE1的水平，这些病例和对照在队列、年龄和献血日期方面进行了匹配。
总体而言，在任何一个队列以及合并分析中，均未观察到乳腺癌风险与循环2-OHE1、16α-OHE1水平或其比值之间存在显著关联。对于2-OHE1，在校正雌酮的模型中，有证据表明按ER状态存在异质性（P≤0.03）。我们观察到2-OHE1与ER+乳腺癌存在保护关联[2-OHE1水平翻倍的多变量校正比值比为0.67（95%置信区间[CI]，0.48 - 0.94；P = 0.02）]。
在本研究中，校正循环雌酮后，较高水平的2-OHE1与绝经后女性ER+乳腺癌风险降低相关。
这些结果表明，在雌激素代谢物与乳腺癌的研究中，考虑母体雌激素水平和ER状态很重要。
