Table 3.
Hazard ratios and 95% confidence intervals for the joint association of polygenic risk score and healthy lifestyle score with overall and lethal prostate cancer in the Health Professionals Follow-up Study and the Physicians’ Health Study.
| PRS quartile | HPFS (n = 10 443) | PHS (n = 1 968) | Pooled (n = 12 411) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Healthy lifestyle score | Healthy lifestyle score | Healthy lifestyle score | |||||||
| Unhealthy (0–2) | Moderate (3) | Healthy (4–6) | Unhealthy (0–2) | Moderate (3) | Healthy (4–6) | Unhealthy (0–2) | Moderate (3) | Healthy (4–6) | |
| HR (95% CI)a | HR (95% CI)a | HR (95% CI)a | HR (95% CI)b | HR (95% CI)b | HR (95% CI)b | HR (95% CI) | HR (95% CI) | HR (95% CI) | |
| Overall prostate cancer | |||||||||
| 75–100% | 1 (Ref.) | 0.97 (0.82–1.16) | 1.01 (0.84–1.22) | 1 (Ref.) | 0.94 (0.57–1.54) | 0.99 (0.60–1.65) | 1 (Ref.) | 0.97 (0.83–1.14) | 1.01 (0.85–1.20) |
| 50–75% | 0.52 (0.41–0.65) | 0.53 (0.44–0.65) | 0.62 (0.50–0.75) | 0.36 (0.19–0.67) | 0.45 (0.27–0.75) | 0.48 (0.28–0.81) | 0.50 (0.40–0.61) | 0.52 (0.44–0.63) | 0.60 (0.49–0.72) |
| 25–50% | 0.28 (0.21–0.36) | 0.31 (0.25–0.38) | 0.37 (0.29–0.46) | 0.18 (0.09–0.38) | 0.33 (0.20–0.57) | 0.28 (0.17–0.48) | 0.26 (0.21–0.34) | 0.31 (0.25–0.38) | 0.35 (0.28–0.43) |
| 0–25% | 0.16 (0.11–0.22) | 0.18 (0.13–0.23) | 0.22 (0.17–0.28) | 0.11 (0.05–0.24) | 0.16 (0.09–0.28) | 0.15 (0.08–0.26) | 0.15 (0.11–0.20) | 0.17 (0.14–0.22) | 0.20 (0.16–0.26) |
| Lethal prostate cancer | |||||||||
| 75–100% | 1 (Ref.) | 0.62 (0.39–0.98) | 0.52 (0.30–0.89) | 1 (Ref.) | 0.60 (0.28–1.31) | 0.63 (0.29–1.34) | 1 (Ref.) | 0.61 (0.41–0.91) | 0.55 (0.36–0.86) |
| 50–75% | 0.51 (0.29–0.89) | 0.47 (0.29–0.76) | 0.45 (0.26–0.78) | 0.45 (0.18–1.17) | 0.33 (0.15–0.73) | 0.31 (0.14–0.69) | 0.49 (0.31–0.80) | 0.42 (0.28–0.64) | 0.40 (0.25–0.63) |
| 25–50% | 0.27 (0.14–0.54) | 0.34 (0.20–0.57) | 0.23 (0.12–0.45) | 0.31 (0.12–0.85) | 0.26 (0.12–0.58) | 0.17 (0.08–0.40) | 0.28 (0.16–0.50) | 0.31 (0.20–0.49) | 0.20 (0.12–0.35) |
| 0–25% | 0.14 (0.06–0.33) | 0.21 (0.11–0.38) | 0.20 (0.10–0.40) | 0.10 (0.03–0.37) | 0.12 (0.05–0.31) | 0.13 (0.06–0.31) | 0.12 (0.06–0.26) | 0.18 (0.11–0.29) | 0.17 (0.10–0.29) |
Abbreviations: CI, confidence interval; HPFS, Health Professionals Follow-up Study; HR, hazard ratio; PHS, Physicians’ Health Study; PRS, polygenic risk score.
HPFS: Inverse probability weighted Cox regression models, stratified by birth cohort and adjusted for age (underlying time-scale), calendar period of inclusion, genetic ancestry (PC1-PC3), lagged PSA screening history, history of other cancers, history of diabetes, current aspirin use, current statin use, and total energy intake.
PHS: Inverse probability weighted Cox regression models, stratified by birth cohort and adjusted for age (underlying time-scale), genetic ancestry (PC1-PC3), history of other cancers, history of diabetes and randomization status.