Polygenic Risk Scores for High-Grade Serous Ovarian Cancer in African American Women within the African American Cancer Epidemiology Study (AACES) Open Access
Kifer, Alexa (Summer 2025)
Abstract
Background:
African American women experience disproportionately poor outcomes from epithelial ovarian cancer (EOC), yet they remain underrepresented in genetic studies that inform risk prediction. Polygenic risk scores (PRS), derived primarily from European ancestry populations, may not accurately capture EOC susceptibility in diverse populations.
Methods:
Using data from the African American Cancer Epidemiology Study (AACES), the largest population-based cohort of African American women with EOC in the U.S., we evaluated a previously developed PRS constructed from 24 genome-wide significant loci. Logistic and multinomial logistic regression models were used to assess associations between standardized PRS and EOC risk, adjusting for age, ancestry, family history, and geographic region. Subtype-specific analyses were conducted to examine histologic variation in genetic risk.
Results:
Among 592 Black women with EOC, a one-unit increase in PRS was associated with significantly increased odds of high-grade serous ovarian cancer (HGSOC) (adjusted OR = 1.37; 95% CI: 1.16–1.62; p = 0.0004). No significant association was observed between PRS and non-HGSOC histotypes. Participants in the top 5% of the PRS distribution had more than twice the odds of HGSOC compared to those in the bottom 80%, indicating a dose-response relationship. These associations persisted after adjusting for potential confounders. Binary logistic models confirmed the robustness and specificity of the PRS to HGSOC.
Conclusions:
This study demonstrates that PRS constructed from European ancestry GWAS data can capture meaningful genetic risk for HGSOC among African American women, despite reduced transferability. These findings underscore the need for ancestry-informed PRS models and inclusive genomic research to advance equitable precision medicine. Incorporating PRS into risk stratification frameworks may improve early detection and prevention efforts for high-risk Black women disproportionately affected by EOC disparities.
Table of Contents
Contents
Abstract………………………………………………………………………………………4
Introduction…………………………………………………………………………………..5
Demographics and Mortality/Survival Rates……………………………………...5
Risk Factors……………………………………………………………………….8
Histologic Variation in Risk Factors………………………………………………11
Prognostic Factors in Risk Factors………………………………………………..13
Genetic Risk Prediction……………………………………………………………16
Materials and Methods…………………………………………………………………….......20
Study Population…………………………………………………………………..20
Data Collection……………………………………………………………………22
Statistical Analysis…………………………………………………………………22
Data Preparation and Quality Control……………………………………………..23
Polygenic Risk Score Construction………………………………………………..24
Logistic Regression Model Construction………………………………………….25
Results…………………………………………………………………………………………..26
Study Population……………………………………………………………………26
PRS Estimates………………………………………………………………………30
Discussion………………………………………………………………………………………..35
References………………………………………………………………………………………..46
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Polygenic Risk Scores for High-Grade Serous Ovarian Cancer in African American Women within the African American Cancer Epidemiology Study (AACES) () | 2025-07-31 13:09:07 -0400 |
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