Risk of aggressive prostate cancer with successive generations in the US among Latino men

Abstract Background US-born Latino men have a higher incidence of prostate cancer than foreign-born Latino men. It was not clear whether these increases were exclusively due to increased detection of prostate cancer in the United States, changes in risk factors of prostate cancer, or a combination of both. Methods In the Multiethnic Cohort we evaluated the association between generational status and risk of prostate cancer in 19 597 Latino men, adjusting for demographic and lifestyle factors and individual- and neighborhood-level socioeconomic status, as well as history of prostate-specific antigen screening. Additional adjustments on polygenic risk score and genetic ancestry were included in the sensitivity analysis in the biorepository cohort with genetic data. Results This analysis included 10 241 first-generation, 4610 second-generation, and 4746 third-generation Latino men, among whom 2366 were diagnosed with prostate cancer during an average of 19.2 years of follow-up. After adjusting for covariates, we observed no association between generational status and risk of overall, localized, or low-grade prostate cancer. A per generation increase was statistically significantly associated with a 13%-15% elevated risk of high-grade, advanced, or aggressive prostate cancer. These associations with aggressive forms of prostate cancer remained statistically significant in the biorepository cohort with additional adjustment on polygenic risk score and genetic ancestry. Conclusions Successive generations in the United States were associated with an increased risk of aggressive forms of prostate cancer among Latino men, and the observed increases cannot be explained by differences in genetic susceptibility, ancestry, prostate-specific antigen screening, lifestyle, or socioeconomic status factors. Further investigations are needed to identify additional factors that contribute to this increased risk.