Table 1.
Associations of 23 known and suspected risk factors and biomarkers with overall breast cancer risk a: Results from Mendelian randomization analyses
| Risk factors b | Number of SNPs | Variance explained (%) | F-statistics | IVW |
MR-PRESSO |
P pleiotropy | ||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | |||||
|
| ||||||||
| Reproductive factors | ||||||||
| Age at menopause (years) | 53 | 5.5 | 75.5 | 1.09 (1.06–1.13) | 2.71×10−7 | 1.11 (1.08–1.14) | 2.53×10−10 | 0.232 |
| Age at menarche (years) | 381 | 7.2 | 67.4 | 0.85 (0.75–0.96) | 0.010 | 0.94 (0.86–1.03) | 0.220 | 0.890 |
| Body weight and other measurements | ||||||||
| BMI (kg/m2) | 856 | 8.3 | 72.4 | 0.96 (0.92–0.99) | 0.023 | 0.97 (0.94–1.00) | 0.069 | 0.880 |
| WHR adj BMI | 440 | 4.3 | 71.1 | 0.92 (0.87–0.97) | 0.002 | 0.91 (0.87–0.95) | 2.85×10−5 | 0.052 |
| Weight at Birth (g) | 57 | 1.7 | 47.3 | 0.90 (0.79–1.03) | 0.145 | 0.93 (0.84–1.02) | 0.124 | 0.322 |
| Height (cm) | 2791 | 41.7 | 177.0 | 1.03 (1.01–1.05) | 0.004 | 1.02 (1.00–1.03) | 0.057 | 0.977 |
| Mammographic dense area (cm2) | 7 | 1.2 | 32.4 | 1.29 (0.97–1.71) | 0.085 | 1.25 (1.09–1.42) | 0.047 | 0.875 |
| Breast size (cup) | 7 | 1.8 | 42.7 | 1.26 (0.83–1.90) | 0.274 | NA | 0.451 | |
| Lifestyle factors | ||||||||
| Physical activity (accelerometer-measured (milligravities)) | 5 | 0.2 | 35.2 | 0.51 (0.26–0.99) | 0.048 | 0.84 (0.61–1.17) | 0.309 | 0.229 |
| Alcohol consumption (drinks per week) | 169 | 1.0 | 33.6 | 1.01 (0.89–1.16) | 0.829 | 0.99 (0.88–1.11) | 0.881 | 0.590 |
| Smoking behavior (lifetime smoking index) | 126 | 1.3 | 48.8 | 1.16 (1.03–1.30) | 0.012 | 1.17 (1.05–1.30) | 0.006 | 0.208 |
| Sleep duration (hours) | 52 | 0.5 | 39.6 | 1.37 (1.11–1.70) | 0.003 | 1.26 (1.10–1.45) | 0.002 | 0.880 |
| Chronotype | 340 | 2.5 | 34.3 | 0.89 (0.83–0.94) | 1.29×10−4 | 0.90 (0.85–0.95) | 1.02×10−4 | 0.324 |
| Biomarkers | ||||||||
| Estrogens (pmol/l) | 3 | 1.6 | 14.3 | 1.14 (1.01–1.28) | 0.030 | NA | 0.970 | |
| Progesterone (nmol/l) | 4 | 10.0 | 35.0 | 1.01 (0.97–1.04) | 0.761 | 1.01 (0.98–1.03) | 0.701 | 0.332 |
| SHBG (nmol/L) | 9 | 3.6 | 38.9 | 0.85 (0.76–0.94) | 0.002 | 0.85 (0.79–0.90) | 0.003 | 0.480 |
| IGF-1 (nmol/L) | 265 | 9.1 | 72.8 | 1.05 (1.00–1.11) | 0.037 | 1.06 (1.02–1.11) | 0.005 | 0.295 |
| Leukocyte telomere length | 19 | 1.5 | 63.6 | 1.19 (1.08–1.32) | 5.63×10−4 | 1.20 (1.11–1.29) | 3.09×10−4 | 0.008 |
| HDL-C (mmol/L) | 528 | 15.9 | 144.5 | 1.10 (1.06–1.15) | 1.12×10−5 | 1.10 (1.06–1.14) | 1.23×10−6 | 0.103 |
| LDL-C (mmol/L) | 218 | 7.9 | 174.0 | 1.05 (0.99–1.11) | 0.083 | 1.02 (0.97–1.07) | 0.407 | 0.020 |
| Triglycerides (mmol/L) | 436 | 11.4 | 130.3 | 0.96 (0.92–1.01) | 0.097 | 0.95 (0.91–0.99) | 0.009 | 0.138 |
| Fasting insulin adj BMI (pmol/L) | 14 | 0.7 | 49.5 | 1.27 (1.03–1.56) | 0.025 | 1.28 (1.10–1.50) | 0.010 | 0.222 |
| 2-h glucose adj BMI (mmol/L) | 9 | 0.9 | 43.4 | 1.28 (0.96–1.72) | 0.098 | 1.07 (0.88–1.31) | 0.534 | 0.005 |
Abbreviation: IVW, inverse-variance weighted; MR, mendelian randomization; PRESSO, pleiotropy residual sum and outlier; BMI, body mass index; WHR, waist-to-hip ratio; HDL-C, high density lipoprotein-cholesterol; LDL-C, low density lipoprotein-cholesterol; IGF-1, insulin like growth factor 1; SHBG, sex hormone binding globulin; NA, not available.
Based on 133,384 breast cancer cases and 113,789 controls.
The unit is in 2 years change per copy of the effect allele for the OR estimates of age at menarche and menopause. The unit is in standard deviation change per copy of the effect allele for the OR estimates of BMI, WHR adj BMI, weight at birth, height, mammographic dense area, physical activity, alcohol consumption, IGF-1, HDL-C, LDL-C, triglycerides, fasting insulin adj BMI, and 2-h glucose adj BMI. The unit is in per-unit change per copy of the effect allele for the OR estimates of breast size, smoking behavior, sleep duration, estrogens, progesterone, SHBG, and leukocyte telomere length. The unit is in per-category change per copy of the effect allele for the OR estimates of chronotype. From definite evening, more evening than morning, don’t know, more morning than evening, and definite morning, which coded as −2, −1,0, 1, and 2.