Background
Prostate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors.
Objective
To examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle.
Design, setting, and participants
We prospectively followed 12 411 genotyped men in the Health Professionals Follow-up Study (1993–2019) and the Physicians’ Health Study (1983–2010). Genetic risk of prostate cancer was quantified using a polygenic risk score (PRS). A healthy lifestyle was defined by healthy weight, vigorous physical activity, not smoking, and a healthy diet.
Outcome measurements and statistical analysis
Overall and lethal prostate cancer events (metastatic disease/prostate cancer–specific death) were analyzed using time-to-event analyses estimating hazard ratios (HRs) and lifetime risks.
Results and limitations
During 27 yr of follow-up, 3005 overall prostate cancer and 435 lethal prostate cancer events were observed. The PRS enabled risk stratification not only for overall prostate cancer, but also for lethal disease with a four-fold difference between men in the highest and lowest quartiles (HR, 4.32; 95% confidence interval [CI], 3.16–5.89). Among men in the highest PRS quartile, adhering to a healthy lifestyle was associated with a decreased rate of lethal prostate cancer (HR, 0.55; 95% CI, 0.36–0.86) compared with having an unhealthy lifestyle, translating to a lifetime risk of 1.6% (95% CI, 0.8–3.1%) among the healthy and 5.3% (95% CI, 3.6–7.8%) among the unhealthy. Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer.
Conclusions
Our findings suggest that a genetic predisposition for prostate cancer is not deterministic for a poor cancer outcome. Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer.
