摘要
目的探讨生育史(生育子女数量、首次生育年龄)与女性激素相关癌症(乳腺癌、子宫内膜癌及卵巢癌)发生风险的因果关联。方法采用单变量和多变量孟德尔随机化(Mendelian randomization,MR)方法,调查生育子女数量(在不孕妇女中为无子女,在正常生育妇女中则为曾生育子女数量)和首次生育年龄与三种女性激素相关癌症的因果效应。采用逆方差加权法作为主要分析方法,采用敏感性分析和可靠性检验以保证主要分析结果的可靠性。结果单变量MR结果显示,与正常生育妇女相比,不孕妇女发生乳腺癌的风险更高[OR=1.07,95%CI(1.05,1.09),P<0.01]。多变量MR结果表明,在正常生育妇女中,考虑了首次生育年龄的影响后,曾生育子女数量越多可能与乳腺癌发生风险降低相关[OR=0.61,95%CI(0.43,0.85),P<0.01]。单变量和多变量MR均未发现首次生育年龄与女性激素相关癌症存在因果关联,且未发现生育子女数量与子宫内膜癌和卵巢癌存在因果关联。敏感性分析和可靠性检验证明结果受到异质性和水平多效性影响的可能性较小。结论正常妇女生育子女越多,乳腺癌发生风险越低;不孕妇女面临更高的乳腺癌发生风险。
Objective To investigate whether there is a causal relationship between reproductive history(number of children,age at first birth)and the risk of hormone-related cancers(breast,endometrial,and ovarian)in women.Methods Univariate and multivariate Mendelian randomization(MR)methods were used to investigate the causal effects of the number of children(childlessness in infertile women and number of children ever born in fertile women)and age at first birth on three hormone-related cancers.The inverse variance weighting method was used for the primary analysis,and sensitivity analyses and reliability tests were used to ensure the reliability of the results.Results Univariate MR showed that infertile women had a higher risk of breast cancer compared with fertile women(OR=1.07,95%CI 1.05 to 1.09,P<0.001).Multivariate MR showed that among fertile women,after accounting for the effect of age at first birth,higher number of children ever born may be associated with lower risk of breast cancer(OR=0.61,95%CI 0.43 to 0.85,P<0.01).Neither univariate nor multivariate MR found a causal relationship between age at first birth and hormonerelated cancers,and no causal relationship was found between the number of children ever born and endometrial and ovarian cancers;sensitivity analyses and reliability tests demonstrated that the results were unlikely to be affected by heterogeneity and horizontal pleiotropy.Conclusion The more children a normal woman has,the lower her risk of breast cancer.Infertile women face a higher risk of breast cancer.
作者
彭庆慧
赵健
林奕蝶
姚强
李紫君
朱彩蓉
PENG Qinghui;ZHAO Jian;LIN Yidie;YAO Qiang;LI Zijun;ZHU Cairong(Department of Epidemiology and Health Statistics,West China School of Public Health,West China Fourth Hospital,Sichuan University,Chengdu 610041,P.R.China;School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen 518055,P.R.China;MRC Integrative Epidemiology Unit,University of Bristol,Bristol BS82BN,UK)
出处
《中国循证医学杂志》
CSCD
北大核心
2024年第8期879-886,共8页
Chinese Journal of Evidence-based Medicine
基金
四川省科技计划项目(编号:2021JDR0189)
国家重点研发计划项目(编号:2016YFC1302505-2)。
关键词
生育史
激素相关癌症
孟德尔随机化分析
因果关系
Reproductive history
Hormone-related cancer
Mendelian randomization analysis
Causality
