前列腺癌是男性癌症死亡的主要原因，迫切需要新的预防策略，其中可能涉及针对具有潜在遗传易感性的男性。探讨遗传风险较高与较低的男性早期前列腺癌死亡风险的差异，为预防提供信息该队列研究对纳入时未患前列腺癌的男性基因分型以及瑞典和美国两项前瞻性队列研究、马尔默饮食与癌症研究 (MDCS) 和健康专业人员随访研究 (MDCS) 中的生活方式数据进行了综合分析。 HPFS），从 1991 年到 2019 年进行随访。数据在 2023 年 4 月到 2024 年 4 月之间进行分析。根据可改变的生活方式行为和遗传风险对男性进行分类。高于中位数的多基因风险评分或有癌症家族史定义男性具有较高的遗传风险（占研究人群的 67%）；其余男性被归类为遗传风险较低。使用事件时间分析法对前列腺癌死亡进行分析，估计风险比 (HR)、绝对风险和按年龄划分的可预防死亡。在纳入分析的 19607 名男性中，中位数(IQR) 纳入时年龄为 59.0 (53.0-64.7) 岁 (MDCS) 和 65.1 (58.0-71.8) 岁 (HPFS)。在随访期间，观察到 107 例早期（75 岁之前）和 337 例晚期（75 岁之后）前列腺癌死亡。与遗传风险较低的男性相比，遗传风险较高的男性早期（HR，3.26；95% CI，1.82-5.84）和晚期（HR，2.26；95% CI，1.70-3.01）前列腺癌死亡率均增加，以及前列腺癌死亡的终生风险较高（3.1% vs 1.3% [MDCS] 和 2.3% vs 0.6% [HPFS]）。 107 例早期前列腺癌死亡中，有 94 例 (88%) 是由遗传风险较高的男性造成的，其中 36% (95% CI, 12%-60%) 据估计可以通过坚持与健康生活方式相关的行为来预防 (95% CI, 12%-60%)。吸烟、健康体重、高体力活动和健康饮食）。在这项为期 20 年的跟踪研究中，具有遗传倾向的男性占早期前列腺癌死亡的绝大多数，其中三分之一估计是可以预防的。这表明遗传风险增加的男性应该成为前列腺癌预防策略的目标。

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.To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts.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.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.Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age.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).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.