Abstract PO-221: Racial differences in frequently mutated protein-coding genes correlates with survival, invasion and metastasis in colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. CRC is caused by mutation in oncogenes, tumor suppressor genes, and genes associated with metastasis and invasion. Understanding mutational signatures in CRC will provide an insight into a specific developmental pathway and pave the way for targeted therapy. Thus, preventing disparity in CRC treatment among racial and ethnic groups. This study aimed to determine the distinct and commonly mutated protein-coding genes of CRC in Whites, African-American and Asian and to evaluate their correlation with survival, invasion and metastasis in CRC. Method: The Cancer Genome Atlas Research Network (TCGA), March, 2021 database on the genomic data commons data portal was queried for frequently mutated protein coding genes. The search was carried out on male and female (ages 34 to 90) colorectal cancer cases in Whites, African-Americans and Asians. The protein coding genes queried are APC, TP53, KRAS, PIK3CA, FAT4, KMT2D, RNF213, ARIDIA, BRAF, TET2, ATM, ZFHX3, FAT1, AMER1, NCOR2, FBXW7, SMAD4, TCFTL2, MYH9, CREBBP, KMT2C, CTNNB1, NRG1, ARAD1B, RNF 43, NF 1, MLLT 4, NIN, KDR, EP 300, PDGFRH, RHOH, ZNF521, MED12, GRIN2A, MECOM and RPL5. Racial differences in protein coding genes in CRC were evaluated using cluster and radar analysis and correlation study for CRC survival, invasion and metastasis pathway were carried using the Pearson correlation with NCSS statistical software. Results: Mutation in APC, TP53, KRAS, PIK3CA, FAT4 and TET-2 with high correlation with inflammation, cell death and survival were common for Whites, African Americans and Asians. African Americans showed distinctive mutation in KMT2C, CTNNB1, NRG1, ARAD1B, RNF 43, NF 1 and MLLT 4 which shows highly positive correlation with proliferation, epithelial mesenchymal transition, adhesion and metastasis. Mutations in NIN, KDR, EP 300, PDGFRH, RHOH, ZNF521, MED12, GRIN2A, MECOM and RPL5 which correlated with cell proliferation and apoptosis was specific for Asians whereas Whites show specific mutation for ARIDIA, TCFTL2 and MYH9 that correlated with chromatin remodeling, hormone function, and cell adhesion. The only mutated gene associated with Black and Asian alone was RNF 43 while Asian and Whites shared mutation in BRAF, ATM and SMAD4. Furthermore, a high level of similarity in mutation was observed for RNF 43, ZFHX3, FAT1, AMER1, FBXW7 and CREBBP. In Conclusion, the racial differences in pathway-based analysis of protein coding genes mutated in colorectal cancer have provided an emerging biomarkers for targeted therapies and chemoprevention of colorectal cancer, thus providing a solution to racial and ethnic disparities associated with cancer treatment and prevention. Citation Format: Babajide Oluwaseun Ajayi, Anuoluwapo Adejoke Adeshina. Racial differences in frequently mutated protein-coding genes correlates with survival, invasion and metastasis in colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-221.