Abstract C154: Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients
Authors: Abubakar Sharafudeen D. , Walch Henry , Bai Xuechun , Agbamu Tejiri , Waters Michele , Arora Kanika , Shah Farheen , Fong Christopher , Jee Justin , Williams Hannah , Berger Michael F , Ganesh Karuna , Aguilar Julio Garcia- , Schultz Nikolaus , Yaeger Rona , Chatila Walid K , Sanchez-Vega Francisco 
Published: September 2024

Background: Colorectal cancer (CRC) patients of African ancestry (AFR) have higher incidence, higher mortality, and shorter overall survival (OS) than patients of non-African ancestry (non-AFR) in the United States. This disparity is likely due to a combination of clinical, genomic, and socioeconomic factors. We investigated real-world data of patients from a single tertiary cancer center to delineate the contribution of each of those variables. Methods: We analyzed data from 3,995 CRC patients, including 247 AFR and 3,748 non-AFR patients, diagnosed after 2014 and treated at Memorial Sloan Kettering Cancer Center. Every patient had a specimen sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Genetic ancestry was determined using previously published methods by our group. Clinical annotations included sex, age at diagnosis (Dx), stage at Dx, and tumor location. Billing records were used to identify the type of insurance per patient and estimate their Yost Index (YI), a location-dependent socioeconomic status (SES) percentile score based on household incomes, house values, rent, poverty, education, and employment statistics. A multivariate cox proportional hazards model was used to assess the association between clinical variables (stage at Dx, age at Dx, sex, primary tumor location), genomic features (MSI status, BRAF, APC, SMAD4 alterations, chromosome 20Q amplifications), SES (YI) and OS. Propensity score matching (PSM) was performed using all features included in the multivariate model to assess outcome differences after matching for clinical, genomic, and socioeconomic variables. OS was measured in months from time of Dx to last follow-up and compared using the log-rank test. Results: AFR patients had worse OS compared to non-AFR patients (median OS: AFR, 44.9 vs. non-AFR, 64.3, p&lt;0.001). AFR patients were younger at Dx (median 53 vs. 57 yo, p&lt;0.001), had higher rates of right-sided tumors (41.1% vs. 30.2%, p&lt;0.001), and less often had microsatellite unstable (MSI) tumors (5.26% vs 10.0%, p=0.014). Among microsatellite stable cases, AFR patients had a higher frequency of KRAS (57.1% vs. 44.7%, p=0.004) and a lower frequency of BRAF mutations (4.3% vs. 7.7%, p=0.069). Medicaid was more frequent among AFR patients (10.12% vs. 4.87%, p&lt;0.001). AFR patients had lower SES (median YI 42 vs. 17, p&lt;0.001). In a multivariate model accounting for clinical, genomic and socioeconomic features, AFR ancestry remained associated with worse outcomes (HR: 1.35, p = 0.007). AFR patients also had significantly shorter OS than the set of non-AFR patients matched for clinical, genomic, and socioeconomic features (5-yr OS was 31.6% for AFR vs 45.7% for non-AFR, log-rank p-value = 0.014). Conclusions: Colorectal cancer patients of AFR ancestry had significantly shorter OS than patients of other ancestries after accounting for basic clinical, genomic, and socioeconomic variables. Further research is needed in order to understand the causes of this disparity.

Citation Format: Sharafudeen D. Abubakar, Henry Walch, Xuechun Bai, Tejiri Agbamu, Michele Waters, Kanika Arora, Farheen Shah, Christopher Fong, Justin Jee, Hannah Williams, Michael F Berger, Karuna Ganesh, Julio Garcia- Aguilar, Nikolaus Schultz, Rona Yaeger, Walid K Chatila, Francisco Sanchez-Vega. Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients [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 C154.