Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk.
Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk.
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DOI：
10.1038/srep15582
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发表时间：
2015-10-26
影响因子：
4.6
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Wang Z;Risch H;Lu L;Irwin ML;Mayne S;Schwartz P;Rutherford T;De Vivo I;Yu H
长期雌激素暴露被认为是子宫内膜癌的主要原因。作为雌激素暴露的可能标志，各种月经和生殖特征，如初潮和绝经年龄，被发现与子宫内膜癌风险有关。为了评估它们对子宫内膜癌的综合影响，我们创建了女性在其一生或研究期间经历的月经周期（TNMC）总数和两个遗传风险评分，初潮年龄GRS1和更年期年龄GRS2。比较482名子宫内膜癌患者和571名对照人群，我们发现TNMC与子宫内膜癌风险相关，并且在调整肥胖和其他潜在混杂因素后，这种关联仍然具有统计学意义。每增加10个月经周期，风险增加约2.5%。该研究还表明，高GRS1与风险增加有关。然而，在调整肥胖因素后，这种关系减弱了。我们的研究进一步表明，高TNMC和GRS1的女性患子宫内膜癌的风险是低这两个指标的女性的两倍。我们的研究结果为雌激素暴露与子宫内膜癌风险有关的遗传背景和生活方式提供了额外的支持。
Prolonged estrogen exposure is believed to be the major cause of endometrial cancer. As possible markers of estrogen exposure, various menstrual and reproductive features, e.g., ages at menarche and menopause, are found to be associated with endometrial cancer risk. In order to assess their combined effects on endometrial cancer, we created the total number of menstrual cycles (TNMC) that a woman experienced during her life or up to the time of study and two genetic risk scores, GRS1 for age at menarche and GRS2 for age at menopause. Comparing 482 endometrial cancer patients with 571 population controls, we found TNMC was associated with endometrial cancer risk and that the association remained statistically significant after adjustment for obesity and other potential confounders. Risk increased by about 2.5% for every additional 10 menstrual-cycles. The study also showed that high GRS1 was associated with increased risk. This relationship, however, was attenuated after adjustment for obesity. Our study further indicated women with high TNMC and GRS1 had twice the risk of endometrial cancer compared to those low in both indices. Our results provided additional support to the involvement of estrogen exposure in endometrial cancer risk with regard to genetic background and lifestyle features.