In mediation analyses combining pairs of mediators into a single model, the effect of fasting insulin on overall endometrial cancer risk attenuated (~40% log OR reduction) when SHBG (a presumed downstream mediator of fasting insulin) was included in the model (OR per increase in natural log transformed pmol/L fasting insulin 2.28, 95% CI 1.34 to 3.86, P = 2.85 × 10−3) (Additional file 1: Table S41). The gene discussed is INS; the disease is endometrial cancer.