A healthy lifestyle in men at increased genetic risk for prostate cancer Journal Article


Authors: Plym, A.; Zhang, Y.; Stopsack, K. H.; Delcoigne, B.; Wiklund, F.; Haiman, C.; Kenfield, S. A.; Kibel, A. S.; Giovannucci, E.; Penney, K. L.; Mucci, L. A.
Article Title: A healthy lifestyle in men at increased genetic risk for prostate cancer
Abstract: 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. Patient summary: This study examined whether the genetic risk of prostate cancer can be attenuated by a healthy lifestyle including a healthy weight, regular exercise, not smoking, and a healthy diet. We observed that adherence to a healthy lifestyle reduced the risk of metastatic disease and prostate cancer death among men at the highest genetic risk. We conclude that men at a high genetic risk of prostate cancer may benefit from adhering to a healthy lifestyle. © 2022 The Authors
Keywords: adult; controlled study; middle aged; human cell; major clinical study; case control study; genetics; cancer risk; follow up; follow-up studies; cancer incidence; prospective study; randomized controlled trial; cohort analysis; genotype; risk factors; medical record review; risk factor; cancer mortality; self report; prostate cancer; prostatic neoplasms; food frequency questionnaire; blood sampling; acetylsalicylic acid; genetic susceptibility; prostate tumor; scoring system; patient compliance; physical activity; genetic risk; risk reduction; hydroxymethylglutaryl coenzyme a reductase inhibitor; disease exacerbation; lifestyle; life style; genotyping; healthy diet; healthy lifestyle; never smoker; lifetime risk; humans; human; male; article; polygenic risk score; genetic risk score; cheek cell; healthy lifestyle score
Journal Title: European Urology
Volume: 83
Issue: 4
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2023-04-01
Start Page: 343
End Page: 351
Language: English
DOI: 10.1016/j.eururo.2022.05.008
PUBMED: 35637041
PROVIDER: scopus
PMCID: PMC10279925
DOI/URL:
Notes: Article -- Source: Scopus
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