Main Session
Sep 29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement

3366 - Polygenic Scores as a Genetically Informed Approach to Prostate Cancer Risk Stratification

02:15pm - 03:30pm ET
Poster Hall - Exhibit Hall A
Screen: 17
POSTER

Presenter(s)

Daniel Sabater Minarim, MS - UCSD Health, La Jolla, CA

D. Sabater Minarim1, A. Dornisch2, R. Karunamuni3, K. M. Morgan4, T. J. Nelson5, C. Teerlink6, J. A. Lynch7, I. Garraway8, V. Million Veteran Prog9, T. M. Seibert3, J. Vassy10, and B. S. Rose2; 1Department of Radiation Medicine and Applied Sciences, UC San Diego Health, San Diego, CA, 2Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 3Research Service, VA San Diego Healthcare System, San Diego, CA, 4Center for Health Equity, Education and Research, University of California San Diego, La Jolla, CA, 5VA San Diego Health Care System, La Jolla, CA, 6Veteran Affairs Medical Center, Salt Lake City, UT, 7Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, 8VA Greater Los Angeles Health System, Los Angeles, CA, 9U.S. Department of Veterans Affairs, Washington, DC, 10VA Boston Healthcare System, Boston, MA, USA, Boston, MA

Purpose/Objective(s): Black or African American (AA) men experience higher prostate cancer (PC) incidence and mortality compared to Non-Hispanic White (NHW) men. We aimed to evaluate whether incorporating polygenic scores improves PC risk stratification and whether they mediate racial disparities in PC diagnosis in a diverse Veteran population.

Materials/Methods: We identified Veterans who underwent their first prostate biopsy from October 1999 to September 2021 using the Veterans Affairs Corporate Data Warehouse, with genetic data from the Million Veteran Program. Patients with prior PC diagnosis, PSA >50 ng/mL, 5a-reductase inhibitor use, or missing covariates were excluded. The cohort included 21,338 men who self-reported as NHW (n=16,447) or Black/AA (n=4,891).

Results: Black/AA men had higher mean PHS601 z-scores compared to NHW men (0.94 vs. -0.27, p<0.001). In the clinical variables only model, Black/AA race was associated with significantly higher odds of cs-PC (OR=1.73, 95% CI: 1.61-1.85, p<0.001). After adding both polygenic scores, the race effect was substantially attenuated (OR=1.07, 95% CI: 0.99–1.16, p=0.099). PHS601 was associated with cs-PC (OR=1.75, 95% CI: 1.69-1.82, p<0.001), while PRS447 was inversely associated (OR=0.69, 95% CI: 0.67-0.72, p<0.001). PHS601 mediated ~90% of this racial disparity (Average Causal Mediation Effect=0.127, 95% CI: 0.119-0.135, p<0.001). The residual direct effect was non-significant (Average Direct Effect=0.014, 95% CI: -0.001-0.031, p=0.072).

Conclusion: The higher rate of cs-PC diagnosis among Black/AA veterans is largely explained by elevated risk as captured by PHS601. These findings support the use of genetically informed screening strategies, replacing self-reported race as a screening determinant with a more precise and interpretable measure of individual risk.