In our study, we observed an association between fasting insulin and endometrial cancer risk, which was in line with results from a Mendelian randomization study (OR for decrease of one SD in genetically determined fasting insulin level 2.34; 94%CI, 1.06–5.14)49 and a suggestion for a mediating effect through fasting insulin, with the point estimate indicating even a larger indirect effect through fasting insulin compared with estradiol. This evidence concerns the gene INS and endometrial cancer.