Table 1.
Two-sample Mendelian randomization results for genetic effect of metformin use on 26 common cancers
| Outcomes | IVs amount | Methods | Beta | Odds ratio | OR_lo95% | OR_up95% | P value | Q-statistics | Ph-value |
|---|---|---|---|---|---|---|---|---|---|
| Gastrointestinal tract cancers | |||||||||
| Colorectal | 24 | MR Egger | − 6.21E+00 | 2.01E−03 | 1.43E−07 | 2.83E+01 | 2.16E−01 | 2.88E+01 | 1.49E−01 |
| Weighted median | − 2.73E+00 | 6.53E−02 | 2.41E−04 | 1.77E+01 | 3.40E−01 | ||||
| IVW | − 2.70E+00 | 6.71E−02 | 1.27E−03 | 3.55E+00 | 1.82E−01 | 2.97E+01 | 1.59E−01 | ||
| Colon | 25 | MR Egger | 6.92E−03 | 1.01E+00 | 9.44E−01 | 1.07E+00 | 8.36E−01 | 2.74E+01 | 2.39E−01 |
| Weighted median | 1.18E−02 | 1.01E+00 | 9.72E−01 | 1.05E+00 | 5.64E−01 | ||||
| IVW | 1.20E−02 | 1.01E+00 | 9.85E−01 | 1.04E+00 | 3.86E−01 | 2.74E+01 | 2.84E−01 | ||
| Rectum | 9 | MR Egger | − 2.11E−01 | 8.09E−01 | 6.33E−01 | 1.04E+00 | 1.36E−01 | 1.04E+01 | 1.68E−01 |
| Weighted median | − 1.43E−02 | 9.86E−01 | 9.50E−01 | 1.02E+00 | 4.49E−01 | ||||
| IVW | − 1.14E−02 | 9.89E−01 | 9.56E−01 | 1.02E+00 | 5.01E−01 | 1.42E+01 | 7.68E−02 | ||
| Liver | 19 | MR Egger | 6.22E−03 | 1.01E+00 | 9.86E−01 | 1.03E+00 | 5.59E−01 | 2.55E+01 | 8.40E−02 |
| Weighted median | − 2.30E−03 | 9.98E−01 | 9.87E−01 | 1.01E+00 | 6.75E−01 | ||||
| IVW | − 3.19E−03 | 9.97E−01 | 9.88E−01 | 1.01E+00 | 4.70E−01 | 2.70E+01 | 7.93E−02 | ||
| Stomach | 24 | MR Egger | − 1.21E+01 | 5.50E−06 | 9.34E−14 | 3.24E+02 | 1.98E−01 | 1.31E+01 | 9.31E−01 |
| Weighted median | − 4.97E+00 | 6.97E−03 | 2.86E−07 | 1.70E+02 | 3.35E−01 | ||||
| IVW | − 2.76E+00 | 6.34E−02 | 3.68E−05 | 1.09E+02 | 4.68E−01 | 1.43E+01 | 9.17E−01 | ||
| Pancreas | 24 | MR Egger | 3.36E+00 | 2.88E+01 | 1.23E−08 | 6.75E+10 | 7.63E−01 | 3.03E+01 | 1.12E−01 |
| Weighted median | 5.58E+00 | 2.64E+02 | 1.25E−03 | 5.59E+07 | 3.73E−01 | ||||
| IVW | 3.47E+00 | 3.21E+01 | 4.92E−03 | 2.10E+05 | 4.39E−01 | 3.03E+01 | 1.42E−01 | ||
| Small intestine | 25 | MR Egger | 3.20E−04 | 1.00E+00 | 9.84E−01 | 1.02E+00 | 9.69E−01 | 1.96E+01 | 6.68E−01 |
| Weighted median | 3.15E−03 | 1.00E+00 | 9.93E−01 | 1.01E+00 | 5.58E−01 | ||||
| IVW | 1.72E−03 | 1.00E+00 | 9.95E−01 | 1.01E+00 | 6.19E−01 | 1.96E+01 | 7.20E−01 | ||
| Larynx | 24 | MR Egger | 3.50E+00 | 3.31E+01 | 1.13E−13 | 9.68E+15 | 8.39E−01 | 2.12E+01 | 5.10E−01 |
| Weighted median | 8.72E+00 | 6.11E+03 | 2.23E−06 | 1.68E+13 | 4.32E−01 | ||||
| IVW | 4.62E+00 | 1.02E+02 | 9.25E−05 | 1.11E+08 | 5.15E−01 | 2.12E+01 | 5.70E−01 | ||
| Oral pharynx | 24 | MR Egger | − 1.72E+01 | 3.26E−08 | 1.66E−25 | 6.38E+09 | 4.05E−01 | 2.26E+01 | 4.24E−01 |
| Weighted median | − 1.16E+01 | 9.10E−06 | 1.35E−16 | 6.11E+05 | 3.61E−01 | ||||
| IVW | − 1.25E+01 | 3.86E−06 | 2.82E−13 | 5.29E+01 | 1.37E−01 | 2.27E+01 | 4.79E−01 | ||
| Oesophagus | 24 | MR Egger | 2.15E+01 | 2.14E+09 | 4.16E−04 | 1.10E+22 | 1.64E−01 | 2.06E+01 | 5.46E−01 |
| Weighted median | 8.05E+00 | 3.14E+03 | 2.61E−05 | 3.79E+11 | 3.96E−01 | ||||
| IVW | 1.15E+01 | 9.51E+04 | 4.68E−01 | 1.93E+10 | 6.60E−02 | 2.11E+01 | 5.73E−01 | ||
| Breast cancers | |||||||||
| Breast cancer | 24 | MR Egger | 6.05E−01 | 1.83E+00 | 2.06E−03 | 1.63E+03 | 8.63E−01 | 3.46E+01 | 4.22E−02 |
| Weighted median | − 1.10E+00 | 3.32E−01 | 1.28E−02 | 8.65E+00 | 5.08E−01 | ||||
| IVW | − 2.26E+00 | 1.05E−01 | 6.17E−03 | 1.77E+00 | 1.18E−01 | 3.59E+01 | 4.18E−02 | ||
| HER(−) | 24 | MR Egger | 3.37E+00 | 2.91E+01 | 3.84E−04 | 2.21E+06 | 5.62E−01 | 3.89E+01 | 1.45E−02 |
| Weighted median | − 1.33E+00 | 2.65E−01 | 1.12E−03 | 6.27E+01 | 6.34E−01 | ||||
| IVW | − 2.00E+00 | 1.36E−01 | 1.23E−03 | 1.50E+01 | 4.06E−01 | 4.08E+01 | 1.26E−02 | ||
| HER(+) | 24 | MR Egger | − 1.16E+00 | 3.14E−01 | 2.35E−04 | 4.19E+02 | 7.55E−01 | 1.63E+01 | 7.99E−01 |
| Weighted median | − 2.42E+00 | 8.88E−02 | 1.11E−03 | 7.09E+00 | 2.79E−01 | ||||
| IVW | − 4.10E+00 | 1.66E−02 | 8.16E−04 | 3.38E−01 | 7.66E−03* | 1.71E+01 | 8.04E−01 | ||
| ER(+) | 24 | MR Egger | 3.59E+00 | 3.61E+01 | 1.33E−01 | 9.78E+03 | 2.23E−01 | 1.15E+02 | 1.68E−14 |
| Weighted median | − 2.00E−01 | 8.19E−01 | 1.18E−01 | 5.68E+00 | 8.40E−01 | ||||
| IVW | − 1.19E+00 | 3.04E−01 | 2.88E−02 | 3.22E+00 | 3.23E−01 | 1.32E+02 | 2.88E−17 | ||
| ER(−) | 24 | MR Egger | 9.72E+00 | 1.67E+04 | 1.25E−01 | 2.22E+09 | 1.21E−01 | 3.25E+01 | 6.90E−02 |
| Weighted median | − 4.86E+00 | 7.73E−03 | 1.87E−05 | 3.20E+00 | 1.14E−01 | ||||
| IVW | − 2.73E+00 | 6.53E−02 | 4.86E−04 | 8.78E+00 | 2.75E−01 | 3.99E+01 | 1.56E−02 | ||
| Lung cancers | |||||||||
| Lung | 25 | MR Egger | − 5.42E−03 | 9.95E−01 | 9.77E−01 | 1.01E+00 | 5.52E−01 | 2.07E+01 | 5.97E−01 |
| Weighted median | − 7.87E−03 | 9.92E−01 | 9.80E−01 | 1.00E+00 | 1.92E−01 | ||||
| IVW | − 6.19E−03 | 9.94E−01 | 9.86E−01 | 1.00E+00 | 1.06E−01 | 2.08E+01 | 6.53E−01 | ||
| NSCLC | 24 | MR Egger | − 2.83E+00 | 5.88E−02 | 2.12E−07 | 1.63E+04 | 6.62E−01 | 2.76E+01 | 0.1910275 |
| Weighted median | − 7.83E−01 | 4.57E−01 | 3.03E−04 | 6.89E+02 | 8.34E−01 | ||||
| IVW | 1.39E−01 | 1.15E+00 | 6.62E−03 | 1.99E+02 | 9.58E−01 | 2.79E+01 | 2.20E−01 | ||
| SCLC | 24 | MR Egger | − 7.91E+00 | 3.66E−04 | 1.26E−18 | 1.06E+11 | 6.46E−01 | 1.93E+01 | 6.29E−01 |
| Weighted median | − 1.29E+01 | 2.53E−06 | 1.97E−15 | 3.24E+03 | 2.28E−01 | ||||
| IVW | − 4.91E+00 | 7.35E−03 | 6.55E−09 | 8.25E+03 | 4.89E−01 | 1.93E+01 | 6.84E−01 | ||
| Skin cancers | |||||||||
| Skin | 16 | MR Egger | − 1.06E−02 | 9.89E−01 | 9.47E−01 | 1.03E+00 | 6.47E−01 | 1.72E+01 | 2.47E−01 |
| Weighted median | − 4.75E−03 | 9.95E−01 | 9.71E−01 | 1.02E+00 | 7.05E−01 | ||||
| IVW | 3.59E−03 | 1.00E+00 | 9.84E−01 | 1.02E+00 | 7.10E−01 | 1.78E+01 | 2.75E−01 | ||
| Melanoma | 24 | MR Egger | 4.95E+00 | 1.42E+02 | 1.05E−18 | 1.92E+22 | 8.36E−01 | 2.36E+01 | 3.70E−01 |
| Weighted median | 2.38E+01 | 2.24E+10 | 1.90E−02 | 2.65E+22 | 9.29E−02 | ||||
| IVW | 5.54E+00 | 2.56E+02 | 1.44E−06 | 4.55E+10 | 5.67E−01 | 2.36E+01 | 4.28E−01 | ||
| Non-melanoma | 24 | MR Egger | − 2.39E+00 | 9.21E−02 | 3.71E−05 | 2.29E+02 | 5.56E−01 | 5.65E+01 | 7.30E−05 |
| Weighted median | − 4.90E−01 | 6.12E−01 | 3.01E−02 | 1.25E+01 | 7.50E−01 | ||||
| IVW | − 6.49E−01 | 5.22E−01 | 2.10E−02 | 1.30E+01 | 6.92E−01 | 5.71E+01 | 1.00E−04 | ||
| Other cancers | |||||||||
| Kidney | 24 | MR Egger | 2.75E+00 | 1.57E+01 | 8.17E−06 | 3.01E+07 | 7.13E−01 | 1.90E+01 | 6.45E−01 |
| Weighted median | 1.48E+00 | 4.40E+00 | 3.98E−04 | 4.87E+04 | 7.55E−01 | ||||
| IVW | 3.07E+00 | 2.15E+01 | 5.05E−02 | 9.11E+03 | 3.21E−01 | 1.90E+01 | 7.00E−01 | ||
| Bladder | 25 | MR Egger | 1.26E−02 | 1.01E+00 | 9.63E−01 | 1.06E+00 | 6.29E−01 | 1.63E+01 | 8.43E−01 |
| Weighted median | 2.67E−02 | 1.03E+00 | 9.93E−01 | 1.06E+00 | 1.24E−01 | ||||
| IVW | 1.88E−02 | 1.02E+00 | 9.97E−01 | 1.04E+00 | 8.65E−02 | 1.64E+01 | 8.75E−01 | ||
| Bone/cartilage | 24 | MR Egger | − 1.34E+00 | 2.61E−01 | 7.12E−21 | 9.56E+18 | 9.54E−01 | 2.70E+01 | 2.11E−01 |
| Weighted median | − 1.95E+00 | 1.42E−01 | 3.60E−12 | 5.58E+09 | 8.75E−01 | ||||
| IVW | − 1.22E+01 | 4.84E−06 | 4.13E−14 | 5.68E+02 | 1.97E−01 | 2.73E+01 | 2.41E−01 | ||
| Thyroid gland | 24 | MR Egger | − 6.72E+00 | 1.20E−03 | 6.00E−10 | 2.40E+03 | 3.74E−01 | 1.89E+01 | 6.54E−01 |
| Weighted median | 4.42E+00 | 8.33E+01 | 7.96E−03 | 8.71E+05 | 3.49E−01 | ||||
| IVW | 1.78E+00 | 5.93E+00 | 1.40E−02 | 2.52E+03 | 5.64E−01 | 2.05E+01 | 6.14E−01 | ||
| Brain | 24 | MR Egger | 6.43E+00 | 6.20E+02 | 5.36E−07 | 7.18E+11 | 5.52E−01 | 1.66E+01 | 7.87E−01 |
| Weighted median | 1.63E+00 | 5.10E+00 | 2.02E−05 | 1.29E+06 | 7.97E−01 | ||||
| IVW | 2.64E−01 | 1.30E+00 | 2.13E−04 | 7.97E+03 | 9.53E−01 | 1.70E+01 | 8.11E−01 | ||
*P value < 0.05; IVW, inverse variance weighted method; OR, odds ratio; OR_lo95%, the lower margin of OR’s 95% confidence interval; OR_up95%, the upper margin of OR’s 95% confidence interval; IVs, instrumental variants; Ph-value, the P value of heterogeneity, heterogeneity existed when Ph-value < 0.05