Healthy lifestyle and prostate cancer risk in the Million Veteran Program
Authors: Pagadala Meghana S. , Lui Asona , Lynch Julie , Karunamuni Roshan , Lee Kyung Min , Plym Anna , Rose Brent S. , Carter Hannah , Kibel Adam S. , DuVall Scott L. , Gaziano J. Michael , Panizzon Matthew S. , Hauger Richard L. , Seibert Tyler M. 
Published: July 2022

AbstractImportanceProstate cancer (PCa) risk is understood to be mostly unmodifiable and inherited, but there is evidence that environmental and behavioral factors may also contribute. A recent study of health professional cohorts suggests a healthy lifestyle can mitigate a high inherited risk of lethal PCa. It is unknown how modifiable factors affect PCa risk in more diverse populations.ObjectiveTo determine the effects of healthy lifestyle on PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population.DesignRetrospective analysis of the Million Veteran Program (MVP), a cohort study conducted 2011-2021.SettingNational, population-based cohort of United States military veterans.ParticipantsAll veterans were eligible to participate. 590,750 male participants were available for this study; 281,923 completed the lifestyle survey.ExposuresSmoking status, exercise (strenuous activity ≥ 2 days per week), family history, race, and ethnicity (all self-reported at enrollment). PSA testing and body mass index (BMI, obtained from clinical records). Genetic risk (assessed via a polygenic hazard score using genotype data).Main OutcomesAge at diagnosis of PCa, diagnosis of metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.ResultsOn univariable analysis, exercise and not smoking were associated with reduced prostate cancer risk (PCa incidence, metastasis, and death), while higher BMI was associated only with reduced PCa death. Not smoking was independently associated with reduced metastatic PCa (HR 0.54, 95% CI 0.49–0.59, p<10−16) and fatal PCa (HR 0.35, 95% CI 0.30– 0.41, p<10−16) when accounting for exercise, BMI, family history, genetic risk, and race/ethnicity. Exercise was not independently associated with any PCa endpoints. Higher BMI was independently associated with reduced fatal PCa (HR 0.97 95% CI 0.96–0.99, p<0.01). Lifetime cause-specific mortality at age 85 was lower for non-smokers (vs. smokers) among Non-Hispanic White men (0.7% vs. 1.8%) and among Black men (1.7% vs. 6.1%).ConclusionsSmoking is independently associated with increased risk of metastatic and fatal PCa among men of diverse race and ethnicity. This demonstrates that lifestyle factors can mitigate the risk of PCa death in high-risk men.Key pointsQuestionIs a healthy lifestyle associated with reduced risk of fatal prostate cancer in a diverse population?FindingsIn a population-based cohort study of 281,923 US military veterans, non-smokers had a slight reduction in risk of being diagnosed with prostate cancer and 0.35 times risk of dying from it, a significant association. Lifetime cause-specific mortality at age 85 was lower for non-smokers among Non-Hispanic White men (0.7% vs. 1.8%) and among Black men (1.7% vs. 6.1%).MeaningMen who smoke are more likely to develop fatal prostate cancer.