Genetic predisposition to female infertility in relation to epithelial ovarian and endometrial cancers

The associations between female infertility and epithelial ovarian cancer (EOC) or endometrial cancer (EC) have been reported in observational studies, but its causal relationship remains unknown. We intended to assess the causal effect of female infertility on EOCs and ECs using a two-sample Mendelian Randomization (MR) approach.

Large pooled genome-wide association study (GWAS) datasets for female infertility (6481 cases and 68 969 controls), EOC (25 509 cases and 40 941 controls), and EC (12 906 cases and 108 979 controls) were derived from public GWAS databases and published studies. The Inverse Variance Weighted method, Weighted Median method, MR-Egger regression, and MR-Pleiotropy Residual Sum and Outlier test were adopted for MR analyses.

Our results suggested that genetically predicted infertility was positively associated with the risk of EOC (OR = 1.117, 95% CI = 1.003-1.245, P = .045), but did not find a causal relationship between infertility and EC (OR = 1.081, 95% CI = 0.954-1.224, P = .223). As to the reverse direction, our study did not obtain evidence from genetics that EOCs (OR = 0.974, 95% CI = 0.825-1.150, P = .755) and ECs (OR = 1.039, 95% CI = 0.917-1.177, P = .548) were associated with an increased risk of infertility.

This large MR analysis supported a causal association between female infertility and increased risk of EOCs, but did not find a causal relationship between infertility and ECs.