Abstract C078: Comprehensive evaluation for contribution of molecular, socioeconomic and disease covariates to colorectal cancer racial survival disparity of 47,178 patients
Authors: Yousef Mahmoud , Yousef Abdelrahman , Zeineddine Mohammad , Chowdhury Saikat , Fanaeian Mohammad , Little-Jackson Naoko , Knafl Mark , Alfaro-Munoz Kristin , Uppal Abinheet , Kopetz Scott , Wang Wenyi , Willis Jason , Shen John Paul 
Published: December 2023

Abstract
Background: Racial disparities in survival of Colorectal cancer (CRC), as well as differing frequency of driver gene mutation, have been observed before. Here we observe that self-reported race is associated with overall survival (OS) in a single institutional cohort of 47,178 patients with CRC. we conducted a systematic investigation of molecular, Socioeconomic (SES) and Disease covariates to quantitate the degree to which each influences OS. Methods: Under an approved IRB protocol, the Palantir-Foundry software system was used to query the MD Anderson (MDA) patient database to identify CRC patients and extract outcomes data and covariates. Genetic mutations that showed significant difference were included with other SES and Disease covariates in Cox-proportional hazard regression model for OS. Preliminary mediation analysis was done to quantify the contribution of each covariate to the OS disparity. Results: 47,178 patients with CRC adenocarcinoma diagnosed between 1973 and 2023 were identified and race (self-reported) was extracted (Asian 1433, 3.0%; African American (AA) 4126, 8.7%; Hispanic 4166, 8.8%; non-Hispanic White (NHW) 37453, 79.4%). Relative to NHW, AA had worse OS (HR=1.22, P= 8.03E-8), while Asians and Hispanics had better OS (HR=0.68, P= 1.06E-8 and HR=0.88, P= 7E-4). Restricting to stage 4 patients, these disparities persisted; AA HR 1.2 (p=1.7E-4) Asian HR 0.67 (p= 1.64E-5), Hispanic HR 0.88 (p= 1.4E-2) relative to NHW. Among 7,628 patients with clinical mutational testing, five genes had significant differences in mutation frequency; APC (45% Asian, 62% AA, 44% NHW, 57% Hispanics, P= 5.83E-3), KRAS (43%, 57%, 44%, 50%, P=3.43E-9), PIK3CA (13%, 23%, 17%, 17%, P=3.37E-3), BRAF (8%, 3%, 8%, 4%, P=1.15E-8), KIT (3%, 2%, 5%, 2%, p=0.046). In multivariate analysis the survival difference between Asians, Hispanics or AA compared to NHW was no longer significant (HR= 0.91, P=0.59, HR= 0.87, P=0.21 and HR=1.14, P= 0.18). In contrast KRAS (HR= 1.5, P=9.22E-9), BRAF (HR= 1.64, P=1E-4) APC mutation (HR= 0.77, P=1E-4) were independently associated with OS, as was higher ECOG (HR= 1.39, P=7.14E-23), higher stage (HR= 1.5, P=3.57E-20), higher national area deprivation index (ADI) quantile (HR=1.08, P= 2.7E-3), being married (HR=1.2, P= 1.52E-2), right side colon tumor (HR=1.22, P= 1.03E-2), poorly differentiated tumors (HR= 1.2, P=1.47E-2), undergoing surgical intervention (HR= 0.47, P=1.54E-29) and MSI-high (HR= 0.41, P=2.16E-6). In our single institution study preliminary mediation analysis showed that ADI, marital status, right sided affection, KRAS mutation, BRAF mutation were the main drivers of the survival disparities in contrast to stage, grade, performance status, surgical intervention and MSI-status. Conclusions: Racial survival disparity is complex and multifactorial. Our single center systematic evaluation showed that SES, driver gene mutations and site of colon affected by the tumor made an important contribution to the racial survival disparity. Further investigation of germline variation, and treatment response is warranted.
Citation Format: Mahmoud Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Saikat Chowdhury, Mohammad Fanaeian, Naoko Little-Jackson, Mark Knafl, Kristin Alfaro-Munoz, Abinheet Uppal, Scott Kopetz, Wenyi Wang, Jason Willis, John Paul Shen. Comprehensive evaluation for contribution of molecular, socioeconomic and disease covariates to colorectal cancer racial survival disparity of 47,178 patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C078.