Reproductive history and risk of hormone-related cancers in women:a Mendelian randomization study
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 hormone-related 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.
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