Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk

• DOI: 10.1001/jamanetworkopen.2024.20034
• Publication Date: 2024-07-03T15:06:05Z
• Authors: Anna Plym; Yiwen Zhang; Konrad H. Stopsack; Emilio Ugalde-Mor...; Tyler M. Seibert; David V. Conti; Christopher A. Ha...; Aris Baras; Tanja Stocks; Isabel Drake; Kathryn L. Penney; Edward Giovannucci; Adam S. Kibel; Fredrik Wiklund; Lorelei A. Mucci
• Keywords: Lower risk

Importance Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective To explore differences in risk early prostate higher vs lower to inform efforts. Design, Setting, and Participants This cohort study used combined analysis genotyped without at inclusion lifestyle data 2 prospective studies Sweden the US, Malmö Diet Cancer Study (MDCS) Health Professionals Follow-Up (HPFS), followed up from 1991 2019. Data were analyzed between April 2023 2024. Exposures Men categorized according modifiable behaviors risk. A polygenic score above median or family history defined (67% population); remaining as being Main Outcomes Measures using time-to-event estimating hazard ratios (HR), absolute risks, preventable deaths by age. Results Among 19 607 included for analysis, (IQR) age was 59.0 (53.0-64.7) years 65.1 (58.0-71.8) (HPFS). During follow-up, 107 (by 75 years) 337 late (after observed. Compared risk, had increased rates both (HR, 3.26; 95% CI, 1.82-5.84) 2.26; 1.70-3.01) death, lifetime risks (3.1% 1.3% [MDCS] 2.3% 0.6% [HPFS]). accounted 94 (88%), 36% (95% 12%-60%) estimated be through adherence associated healthy (not smoking, weight, high physical activity, diet). Conclusions Relevance In this 20-year follow-up study, predisposition vast majority deaths, one-third preventable. suggests that should targeted strategies.