女性雌激素与乳腺癌发病和死亡风险因果关联的孟德尔随机化研究  

Causal associations of female estrogen with the risk of incidence and mortality of breast cancer:a Mendelian randomization study

作　　者：李增俊 林奕蝶 陈海畅 田韫菏 赵健 朱彩蓉 LI Zeng-jun;LIN Yi-die;CHEN Hai-chang;TIAN Yun-he;ZHAO Jian;ZHU Cai-rong(West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,China;不详)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院流行病学与卫生统计学系,四川成都610041 [2]南方科技大学公共卫生及应急管理学院

出　　处：《现代预防医学》2024年第6期1012-1016,1031,共6页Modern Preventive Medicine

基　　金：四川省科技计划项目(2021JDR0189);中国主要恶性肿瘤的危险因素监测及控制关键技术研究(2016YFC1302505-2)。

摘　　要：目的探索雌激素与女性乳腺癌发病和死亡风险的关系。方法使用公开发表的全基因组关联研究汇总数据,以雌二醇代表雌激素,将与雌二醇相关的遗传位点作为工具变量,采用单变量孟德尔随机化(逆方差加权法)方法,评估雌激素(雌二醇)与女性乳腺癌及其亚型的发病风险(4项指标)和死亡风险(6项指标)间的因果关联。结果雌二醇水平较高(≥175 pmol/L)会增加乳腺癌(不分型)的发病风险(OR=1.43,95%CI:1.27~1.60,P=2.92×10^(-9));雌二醇水平较高也是雌激素受体阴性乳腺癌(OR=1.41,95%CI:1.25~1.60,P=2.16×10^(-8))与雌激素受体阳性乳腺癌(OR=1.49,95%CI:1.29~1.72,P=6.92×10^(-8))发病的危险因素;未发现雌二醇与三阴性乳腺癌发病风险的因果关联;未发现雌二醇与乳腺癌及其亚型死亡风险的因果关联。结论雌激素水平较高(≥175 pmol/L)是乳腺癌(不分型)、雌激素受体阴性与雌激素受体阳性乳腺癌发病的危险因素。Objective To investigate the causal association between estrogen and breast cancer incidence and mortality risk.Methods Using summary data from genome-wide association studies,with estradiol representing estrogen,genetic variants associated with estradiol were utilized as instrument variables.Employing the univariate Mendelian randomization method,the causal association between estradiol and the risk ofincidence(4 outcomes),as well as the risk of mortality(6 outcomes)of female breast cancer and its subtypes,were assessed by the inverse variance-weighted method.Results The results revealed that elevated levels of estradiol(≥175 pmol/L)were associated with an increased risk of overall breast cancer(OR=1.43,95%CI:1.27-1.60,P=2.92×10^(-9)),estrogen receptor-negative breast cancer(OR=1.41,95%CI:1.25-1.60,P=2.16×10^(-8)),and estrogen receptor-positive breast cancer(OR=1.49,95%CI:1.29-1.72,P=6.92×10^(-8))incidence.However,there was no evidence that elevated levels of estradiol were the risk factors for triple-negative breast cancer incidence.Moreover,overall breast cancer and its subtypes mortality risks were not shown to be causally related to estradiol.Conclusion Elevated estrogen levels(≥175 pmol/L)are associated with an increased risk of overall breast cancer,estrogen receptor-negative breast cancer,and estrogen receptor-positive breast cancer incidence.

关 键 词：孟德尔随机化 雌激素 乳腺癌亚型 乳腺癌发病风险 乳腺癌死亡风险 

分 类 号：R737.9[医药卫生—肿瘤]