Abstract B060: Health disparities and the molecular genomics of colorectal cancer by ancestry: The translational impact on colorectal cancer screening, surveillance, and treatment
Authors: Thompson Taylor , Greally John , Myer Parvathi 
Published: August 2020

Background: African Americans with colorectal cancer (CRC) have significantly worse outcomes than Caucasians with higher incidence, later stage at presentation, and worse overall survival. Even when controlling for socioeconomic status and stage at presentation, African Americans compared to Caucasians have a poorer response to medical therapy. We hypothesized that African Americans with colorectal cancer have a distinct genomic mutational profile that explains the observed differences in the natural history and response to treatment. Furthermore, self-reported data on race are imprecise, especially in individuals of mixed race as often found in under-represented communities.

Methods: Using unpublished data from The Cancer Genome Atlas (TCGA), we utilized genomic data to accurately capture a person's ancestry (i.e., European, African, Asian). For each patient with CRC, we used a microarray of single-nucleotide polymorphisms (SNPs) and matched their genome with the publicly available 1000 Genomes project, which is a well-characterized database of the major world populations. Each individual's self-reported race was reclassified using a microarray of their SNPs using Ancestry Informative Markers with Principal Component Analysis. After genotypically defining each individual's ancestry, we studied differences in their somatic mutational profiles. To determine somatic mutational variations, we utilized MuTect2 software to study whole-exome sequencing data of the tumor and normal tissue. The functional impact of each mutation was then classified as high or low. Somatic mutation results were separated based on mutation type (e.g., single-nucleotide variants or insertions/deletions). Mutation-specific tables were separated by genotypically defined race. Permutation analysis was performed using 1000 random samplings to determine whether the observed gene frequency for each race was statistically significant (p &lt;0.05).

Results: 633 patients with colorectal cancer were analyzed and their baseline characteristics were: females (62%), self-reported African Americans (10%) and Caucasians (47%), stage III/IV (35%) and proximal CRC (50%). Preliminary data reveal unique somatic mutations that were distinct in individuals from African ancestry with specific genes playing key roles in oncogenesis. Additional data, including genotypically defined ancestry and somatic mutational differences, will be reported at the time of the conference.

Conclusions: To our knowledge, this is the first application of ancestry informative markers using whole-exome sequencing to study health disparities in colorectal cancer. Differences in tumor mutational profiles may help explain disparities in outcomes between individuals of European and African ancestry.

Citation Format: Taylor Thompson, John Greally, Parvathi Myer. Health disparities and the molecular genomics of colorectal cancer by ancestry: The translational impact on colorectal cancer screening, surveillance, and treatment [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B060.