Abstract PR014: Increasing risk of prostate cancer with successive generations in the US among Latino men in the Multiethnic Cohort

Abstract Background: US-born Latino men have a higher incidence of prostate cancer (PCa) than foreign-born Latino men. It is unclear whether this increase in PCa incidence was due to increased detection of PCa, differences in risk factors of PCa, or a combination of both. In this prospective study, we investigated the association of generational status with PCa risk in Latino men and assessed whether such association can be explained by differences in genetic susceptibility, history of prostate-specific antigen (PSA) screening, lifestyle factors, and/or individual and neighborhood socioeconomic status (SES) measures across generations. Methods: This study was conducted in 6,458 men self-reported as Latino or Hispanic in the Multiethnic Cohort (MEC), of which 2,114 were first-generation (foreign-born), 1,410 were second-generation (US-born with foreign-born parents), and 1,516 were third- generation (US-born with at least one US-born parent). The association between generational status and risk of PCa (overall and subtypes by grade and stage) was assessed using Cox models adjusting for age, family history of PCa, polygenic risk score (PRS) of PCa, the top ten principal components, history of PSA screening, body mass index, history of diabetes, smoking status, education attainment, neighborhood SES and ethnic enclave. Results: Among the 6,458 Latino men in the MEC, a total of 579 PCa were diagnosed during 12.8 years of average follow-up, including 429 low-grade (Gleason score <=7), 108 high-grade (Gleason score >7), 393 localized, 94 advanced, 167 aggressive (high-grade or advanced), and 70 lethal (metastatic or PCa-specific death) PCa. The age-adjusted incidence rate of PCa (per 100,000) was 350.1 in first-generation, 503.5 in second-generation, and 447.2 in third-generation Latino men. With successive generations in the US, there was an increase in education attainment, history of PSA screening, and residence in high neighborhood SES areas. First-generation Latino men were also more likely to reside in high ethnic enclave neighborhoods, compared with second- and third- generation Latino Americans. Adjusting for the abovementioned covariates did not lead to substantial changes in the association between generational status and risk of PCa. In the fully adjusted model, one generation increase was suggestively associated with an 11% higher risk of total PCa (95% CI=0.99-1.24, P=0.07). This association was more profound for aggressive disease where the increase in risk was 29% for high-grade PCa (95% CI=1.00-1.66, P=0.05), 24% for aggressive PCa (95% CI=1.01-1.52), and 39% for lethal PCa (95% CI=1.02-1.90, P=0.04). Conclusions: Increasing generational status of Latino men was associated with a higher risk of PCa, especially for aggressive disease. The observed increase in risk of PCa by generational status cannot be explained by differences in genetic susceptibility, PSA screening, lifestyle, and SES factors. Further investigations are needed to identify additional factors that contribute to this increased risk. Citation Format: Fei Chen, Adelynn Paik, Xin Sheng, Iona Cheng, Salma Shariff-Marco, Lynn R. Wilkens, Loïc Le Marchand, David V. Conti, Christopher A. Haiman, Veronica Wendy Setiawan. Increasing risk of prostate cancer with successive generations in the US among Latino men in the Multiethnic Cohort [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR014.