Table 2.

Mendelian randomization studies assessing the causal relationship between putative risk factors and endometrial cancer risk

Trait assessed (number of variants used inrisk score)Number of casesNumber of controlsAssociation resultsCommentsReference
Type 2 Diabetes (49 variants)1,2878,2730.91 (0.79–1.04); P = 0.16Endometrioid endometrial cancer cases only(30)
Increased fasting glucose (36 variants)1,2878,2731.00 (0.67–1.50); P = 0.99Endometrioid endometrial cancer cases only(30)
Increased fasting insulin (18 variants)1,2878,2732.34 (1.06–5.14); P = 0.03Endometrioid endometrial cancer cases only(30)
Early insulin secretion (17 variants)1,2878,2731.40 (1.12–1.76); P = 0.003Endometrioid endometrial cancer cases only(30)
BMI (32 variants)1,2878,2733.86 (2.24–6.64); P = 1 × 10−6Endometrioid endometrial cancer cases only(30)
BMI (97 variants)3,3763,8671.13 (1.04–1.22); P = 0.002Endometrioid endometrial cancer cases only. Association did not persist after adjustment for measured BMI.(65)
BMI (77 variants)6,60937,9262.011 (1.94–2.28); P = 3.4 × 10−17All endometrial cancer cases. Remained significant after adjustment for measured BMI (OR 1.23; P = 5.3 × 10−4).(29)
Waist–hip ratio (34 variants)6,60937,9261.02 (0.99–1.04); P = 0.09All endometrial cancer cases. Waist–hip ratio variants are those that were associated with this trait among women.(29)
Waist–hip ratio (47 variants)6,60937,9260.97 (0.63–1.31); P = 0.86All endometrial cancer cases. Waist–hip ratio variants are those that were associated with this trait in men and women.(29)
Serum estradiol level (1 variant)6,60837,9251.15 (1.11–1.21); 4.8 × 10−11All endometrial cancer cases. CYP19A1 variant rs727478 used to predict serum estradiol level (10% increase per A-allele).(17)
Menarche (age of onset) (237 variants)6,60937,9260.78 (0.70–0.87); P = 1.0 × 10−5All endometrial cancer cases. Menarche variants were adjusted for genetically predicted BMI.(32)
Adult height (814 variants)12,906108,9791.00 (0.95–1.06); P = 0.90All endometrial cancer cases.(24)