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

Autor:	Plym A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Zhang Y; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts., Stopsack KH; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston., Ugalde-Morales E; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Seibert TM; Department of Radiation Medicine and Applied Sciences, Department of Radiology, and Department of Bioengineering, University of California San Diego, La Jolla., Conti DV; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles., Haiman CA; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles., Baras A; Regeneron Genetics Center, Tarrytown, New York., Stocks T; Department of Translational Medicine, Lund University, Malmö, Sweden., Drake I; Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.; Skåne University Hospital, Malmö, Sweden., Penney KL; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Giovannucci E; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Kibel AS; Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Wiklund F; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Mucci LA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2024 Jul 01; Vol. 7 (7), pp. e2420034. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1001/jamanetworkopen.2024.20034
Abstrakt:	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 of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts. Design, Setting, and Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024. Exposures: Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk. Main Outcomes and Measures: Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age. Results: Among the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet). Conclusions and Relevance: In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu