There was evidence for a mediating role of bioavailable testosterone (15% mediated, 95% CI 10 to 20%, P = 1.43 × 10−8), fasting insulin (11% of total effect mediated, 95% CI 1 to 21%, P = 2.89 × 10−2) and SHBG (7% mediated, 95% CI 1 to 12%, P = 1.81 × 10−2) in the relationship between BMI and overall endometrial cancer risk (Table 5). The gene discussed is INS; the disease is endometrial cancer.