TABLE 3.
Multivariable RRs and 95% CIs of breast cancer according to quartiles of polygenic risk score.
| Q1, ←0.8 | Q2, −0.8 to ←0.4 | Q3, −0.4 to <0.03 | Q4, ≥0.03 | P-trend | P-heterogeneity | |
|---|---|---|---|---|---|---|
| Overall breast cancer† | ||||||
| Cases/controls, n | 211/424 | 386/424 | 443/423 | 897/424 | ||
| RR (95% CI) | 1.00 (ref) | 1.80 (1.44–2.23) | 2.01 (1.69–2.61) | 4.04 (3.29–4.96) | <0.0001 | 0.001 |
| ER-positive breast cancer† | ||||||
| Cases/controls, n | 135/424 | 264/424 | 312/423 | 673/424 | ||
| RR (95% CI) | 1.00 (ref) | 1.91 (1.50–2.45) | 2.31 (1.81–2.96) | 4.84 (3.85–6.12) | <0.0001 | |
| ER-negative breast cancer‡ | ||||||
| Cases/controls, n | 48/424 | 64/424 | 65/424 | 111/424 | ||
| RR (95% CI) | 1.00 (ref) | 1.30 (1.06–1.60) | 1.65 (1.35–2.02) | 2.55 (2.10–3.10) | <0.0001 | |
Data are from the NHS and NHSII. Models are adjusted for age at blood draw (continuous), BMI at blood draw (continuous), family history (yes vs. no), history of benign breast disease (yes vs. no), alcohol consumption (non-drinker, <5 g/day, 5–10 g/day, 10–15 g/day, or 15+ g/day), age at first birth/parity (nulliparous; 1 or 2 children and <25 years old; 1 or 2 children and 25–29 years old; 1 or 2 children and 30+ years old; 3+ children and <25 years old; or 3+ children and 25+ years old), menopausal status (premenopausal, postmenopausal, or unknown), age at menarche (11 years or younger, 12 years, 13 years, or 14+ years), and smoking status (never, former, or current). RRs and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors; tests for trend were conducted using the Wald test, where the medians of the quartiles were modeled continuously. †The standardized PRS score for overall and ER-positive breast cancer is based on 313 SNPs with overall and subtype specific weights. ‡The standardized PRS score for ER-negative breast cancer is based on 313 SNPs with subtype specific weights. Abbreviations: ER, estrogen receptor; MD, mammographic density; NHS, Nurses' Health Study; NHSII, second cohort of the Nurses' Health Study; PRS, polygenic risk score.