This study employs a two-sample Mendelian randomization (MR) approach to investigate the causal relationship between increased Body Mass Index (BMI) and four characteristic female cancers.

BMI and data pertaining to the four characteristic female cancers were obtained from the GWAS database. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) based on assumptions. The PhenoScanner method was utilized to eliminate SNPs associated with confounding factors. Five Mendelian randomization analysis methods were employed for two-sample Mendelian randomization analysis, including inverse variance-weighted (IVW). Cochran Q and Rücker Q heterogeneity tests were conducted using IVW and MR-Egger methods. The egger-intercept method was employed for pleiotropy testing, and stepwise exclusion testing was used for sensitivity analysis. F-values were calculated to assess the presence of weak IVs bias.

Genetically predicted increase in BMI was causally associated with reduced risk of breast cancer (OR=0.648, 95% CI: 0.535-0.783, P=7.74e-06) and increased risk of endometrial cancer (OR=1.534, 95% CI: 1.195-1.970, P=7.84e-04).

BMI may potentially decrease the risk of female breast cancer while increasing the risk of endometrial cancer. There is inadequate evidence to indicate a significant impact of increased BMI on the occurrence risk of other characteristic female cancers studied. Further research is warranted to elucidate these findings.