Serum prostate-specific antigen levels and prostate cancer risk in a multiethnic population

Purpose: While prostate-specific antigen (PSA) is the most commonly used biomarker for prostate cancer (PCa) screening, multiple studies in the U.S. and Europe have shown that PSA levels in midlife, many years before a PCa diagnosis, are associated with increased risk of PCa later in life. However, limited information is available on the relationship between PSA levels measured years before diagnosis and risk of PCa in non-White populations. Methods: We examined whether a PSA level in older adult men measured up to 10+ years before a PCa diagnosis is associated with risk of overall PCa and aggressive PCa (Gleason score>7, non-localized disease, or death from PCa) in a nested case-control study of African American (AA), Latino (LA), Japanese (JP), Native Hawaiian (NH), and Non-Hispanic White (WH) men in the Multiethnic Cohort (MEC). Pre-diagnostic blood levels of total PSA were measured among 2,245 incident PCa cases and 2,203 age and ancestry matched controls. We also assessed the discriminative ability of PSA, years before diagnosis, relative to a polygenic risk score (PRS) for PCa. Results: The mean age at blood draw when PSA was measured for cases and controls was 68 (range: 47-86) and 69 (47-87), respectively. Among cases, the average duration between blood draw and a PCa diagnosis was 4.9 years (range: <1 year to 18 years). Compared to men with PSA below the median, men with PSA above the median had odds ratios (ORs) (95% CIs) for total PCa of 26.15 (16.73-40.87), 7.56 (5.60-10.22) and 3.67 (2.40-5.61), when measured <5, 5-10, and 10+ years before a PCa diagnosis, respectively. The magnitude of the associations were similar for aggressive disease. In men with PSA measured <5, 5-10 and 10+ years before a diagnosis, 95%, 89% and 75% of total PCa cases, respectively, were found to occur among men with a PSA level above the median, while 58%, 28% and 19% of cases, respectively, occurred among men with a PSA level in the top 10^th percentile. By race/ethnicity group, the percentages of cases occurred among men with a PSA level above the median measured <5, 5-10 and 10+ years before a diagnosis were: 98%, 89%, 76% in AA; 93%, 90%, 80% in LA; 95%, 91%, 80% in JP; 96%, 95%, 69% in NH, and; 95%, 82%, 65% in WH, respectively. In analysis of the PRS, 25% of cases occurred among those in the top 10^th percentile of the PRS distribution. At 10+ years, the independent effect of PSA on total PCa (OR per SD increase: 1.88, CI: 1.45-2.46) was comparable to the independent effect of the PRS (OR per SD increase: 2.12, CI: 1.55-2.93) in a model that mutually adjusted the effects of both PSA and PRS. Conclusions: Our findings in this study among older men suggest that PSA is informative as a marker of risk within 10 years of diagnosis, whereas the PRS can be used to define a man9s risk earlier in life. Citation Format: Alisha Chou, Burcu F. Darst, Lynne R. Wilkens, Loïc Le Marchand, Hans G. Lilja, David V. Conti, Christopher A. Haiman. Serum prostate-specific antigen levels and prostate cancer risk in a multiethnic population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-16.