Table 1.
Mendelian randomization studies on endometrial cancer.
| Author [ref], year | Exposure | Outcome | Sample size for the outcome data | Sources | SNPs | Estimate (95% CI) | MR methods | |
|---|---|---|---|---|---|---|---|---|
| Cases | Control | |||||||
| Prescott et al, 2015 (38) | BMI | EC | 3376 | 3867 | Epidemiology of Endometrial Cancer Consortium | 97 | 1.13 (1.04 to 1.22) | Pooled unconditional logistic regression |
| Nead et al, 2015 (39) | T2D | EC | 1287 | 8273 | Studies from the UK and Australia | 49 | 0.91 (0.79 to 1.04) | IVW |
| Fasting glucose | 36 | 1.00 (0.67 to 1.50) | ||||||
| Fasting insulin | 18 | 2.34 (1.06 to 5.14) | ||||||
| Early insulin secretion | 17 | 1.40 (1.12 to 1.76) | ||||||
| BMI | 32 | 3.86 (2.24 to 6.64) | ||||||
| Painter et al, 2016 (40) | BMI | EC | 6609 | 37926 | ECAC | 77 | 2.11 (1.94 to 2.28) | IVW |
| Endometrioid EC | 2.27 (2.08 to 2.45) | |||||||
| Waist-hip ratio | EC | 47 | 0.97 (0.63 to 1.31) | |||||
| Thompson et al, 2016 (41) | Estradiol | EC | 6608 | 37925 | ECAC | 105 | 1.09 (1.03 to 1.21) | |
| Day et al, 2017 (42) | Age at menarche | EC | 4401 | 28758 | ECAC | 375 | 0.781 (0.699 to 0.872) | IVW |
| Haycock et al, 2017 (43) | Telomere Length | EC | 6608 | 37925 | ECAC | 12 | 1.31 (1.07 to 1.61). | IVW |
| Kho et al, 2019 (44) | Selenium | EC | 12906 | 108979 | ECAC | 4 | 0.99 (0.87 to 1.14) | Wald-type ratios/IVW |
| Ong et al, 2019 (45) | Coffee | EC | 373 | 85999 | UK Biobank | 4 | 0.963 (0.912 to 1.018) | IVW |
| Yuan et al, 2020 (46) | TNF | EC | 1520 | 366123 | UK Biobank | 3 | 0.25 (0.07 to 0.94) | IVW |
| Dimou et al, 2020 (47) | Adiponectin | EC | 12906 | 108979 | ECAC | 18 | 1.02 (0.89 to 1.17) | IVW |
| Leptin | 2 | 1.46 (0.69 to 3.06) | ||||||
| sOB-R | 4 | 1.02 (1.00 to 1.05) | ||||||
| PAI-1 | 4 | 1.38 (1.04 to 1.82) | ||||||
| Ruth et al, 2020 (48) | Testosterone | EC | 12,270 | 46,126 | ECAC | 254 | 1.39 (1.26 to 1.53) | IVW |
| Endometrioid EC | 1.39 (1.24 to 1.55) | |||||||
| Non-endometrioid EC | 1.26 (0.99 to 1.61) | |||||||
| Sex hormone-binding globulin | EC | 359 | 0.77 (0.67 to 0.89) | |||||
| Endometrioid EC | 0.78 (0.67 to 0.91) | |||||||
| Non-endometrioid EC | 0.78 (0.55 to 1.11) | |||||||
| Yuan et al, 2020 (49) | T2D | EC | 1931 | 292606 | UK Biobank | 399 | 1.08 (1.01 to 1.15) | IVW |
| Masuda et al, 2021 (50) | BMI | EC | 909 | 39556 | BioBank Japan Project | 74 | 1.22 (1.08 to 1.38) | IVW |
| 194174 | UK Biobank | 131 | 1.0008 (1.0002 to 1.0014) | |||||
| Kho et al, 2021 (51) | LDL cholesterol | EC | 12906 | 108979 | ECAC | 141 | 0.90 (0.85 to 0.96) | IVW |
| Endometrioid EC | 8758 | 46126 | 142 | 0.93 (0.87 to 1.01) | ||||
| Non-endometrioid EC | 1230 | 35447 | 144 | 0.76 (0.63 to 0.90) | ||||
| HDL cholesterol | EC | 12906 | 108979 | 168 | 1.06 (0.99 to 1.13) | |||
| Endometrioid EC | 8758 | 46126 | 168 | 1.02 (0.95 to 1.10) | ||||
| Non-endometrioid EC | 1230 | 35447 | 169 | 1.20 (1.00 to 1.45) | ||||
| Triglycerides | EC | 12906 | 108979 | 114 | 0.98 (0.90 to 1.06) | |||
| Endometrioid EC | 8758 | 46126 | 115 | 0.96 (0.87 to 1.05) | ||||
| Non-endometrioid EC | 1230 | 35447 | 116 | 1.15 (0.90 to 1.45) | ||||
| Ahmed et al, 2021 (52) | Adiposity | EC | 1208 | 145748 | UK Biobank | 127 | 1.77 (1.16 to 2.68) | IVW |
| Freuer et al, 2021 (53) | BMI | EC | 12270 | 46126 | ECAC, E2C2 | 297 | 1.75 (1.57 to 1.95) | IVW |
| AFR | 116 | 1.43 (1.24 to 1.65) | ||||||
| TFR | 202 | 1.01 (0.92 to 1.11) | ||||||
| LFR | 166 | 0.99 (0.93 to1.03) | ||||||
| Larsson et al, 2021 (54) | Plasma cortisol | EC | 12906 | 108979 | ECAC | 3 | 1.50 (1.13 to 1.99) | IVW |
| 879 | FinnGen consortium | |||||||
| Mullee et al, 2021 (55) | Total testosterone | EC | 12906 | 108979 | ECAC | 1.38 (1.22 to 1.57) | IVW | |
| Free testosterone | 2.07 (1.66 to 2.58) | |||||||
| SHBG | 0.76 (0.67 to 0.86) | |||||||
| IGF-1 | 0.98 (0.90 to 1.07) | |||||||
| Larsson et al, 2021 (56) | Endogenous 17β-estradiol | EC | 12906 | 108979 | ECAC | 5 | 1.09 (1.06 to 1.11) | IVW |
| Endometrioid EC | 8758 | 46126 | 1.10 (1.07 to 1.13) | |||||
| Non-endometrioid EC | 1230 | 35447 | 1.02 (0.96 to 1.08) | |||||
| Kho et al, 2021 (57) | Endometriosis | EC | 12270 | 46426 | ECAC | 26 | 1.09 (0.92 to 1.31) | IVW |
| PCOS | 14 | 0.95 (0.88 to 1.03) | ||||||
| Uterine fibroids | 23 | 1.19 (1.03 to 1.36) | ||||||
| O’Mara et al, 2021 (58) | BMI | EC | 12906 | 108979 | ECAC | 77 | 1.92 (1.63 to 2.25) | IVW |
| Endometrioid EC | 8758 | 46126 | 2.04 (1.69 to 246) | |||||
| Non-endometrioid EC | 1230 | 35447 | 1.65 (1.13 to 2.41) | |||||
| Waist:hip ratio | EC | 12906 | 108979 | 47 | 0.95 (0.72 to 1.25) | |||
| Endometrioid EC | 8758 | 46126 | 0.94 (0.71 to 1.24) | |||||
| Non-endometrioid EC | 1230 | 35447 | 1.27 (0.69 to 2.33) | |||||
| Age at menarche (years); total effect | EC | 12906 | 108979 | 368 | 0.82 (0.77 to 0.87) | |||
| Endometrioid EC | 8758 | 46126 | 0.80 (0.74 to 0.86) | |||||
| Non-endometrioid EC | 1230 | 35447 | 0.93 (0.79 to 1.08) | |||||
| Age at menarche (years); direct effect | EC | 12906 | 108979 | 368 | 0.88 (0.82 to 0.94) | |||
| Endometrioid EC | 8758 | 46126 | 0.86 (0.79 to 0.93) | |||||
| Non-endometrioid EC | 1230 | 35447 | 0.97 (0.82 to 1.16) | |||||
| Age at natural menopause (years) | EC | 12906 | 108979 | 54 | 1.03 (1.00 to 1.06) | |||
| Endometrioid EC | 8758 | 46126 | 1.02 (0.99 to 1.06) | |||||
| Non-endometrioid EC | 1230 | 35447 | 1.07 (0.99 to 1.14) | |||||
| Height | EC | 12906 | 108979 | 814 | 1.00 (0.95 to 1.06) | |||
| Endometrioid EC | 8758 | 46126 | 0.99 (0.93 to 1.05) | |||||
| Non-endometrioid EC | 1230 | 35447 | 1.00 (0.88 to 1.15) | |||||
SNPs, single nucleotide polymorphisms; BMI, body mass index; EC, endometrial cancer; T2D, type 2 diabetes mellitus; IVW, Inverse-variance weighted; ECAC, Endometrial cancer Association Consortium; PAI-1, plasminogen activator inhibitor-1; sOB-R, soluble leptin receptor; LDL, low-density lipoprotein; HDL, high-density lipoprotein; AFR, arm fat ratios; TFR, trunk fat ratios; LFR, leg fat ratios; IGF-1, insulin-like growth factor-1; PCOS, polycystic ovary syndrome.