Abstract 104: Racial and ethnic differences in genomic profiling of early onset colorectal cancer
Authors: Hein David M. , Deng Weiye , Kazmi Syed A. , Jones Amy L. , Kainthla Radhika , Cantarel Brandi , Sanford Nina N. 
Published: July 2021

Introduction: Incidence and mortality of early onset colorectal cancer (EOCRC), defined as CRC diagnosed prior to 50, are rising, with some studies showing distinct race/ethnic trends. Although reasons are likely multifactorial, genomic differences may play a role. We examined tumor genomic profiles across race/ethnicity in a diverse cohort of EOCRC patients. Procedures: Next generation sequencing data from Memorial Sloan Kettering Cancer Center (MSK341, MSK410, MSK468) and Dana-Farber Cancer Institute (DFCI1, DFCI2, DFCI3) was pulled from AACR Project GENIE (v8.1). Due to limited racial/ethnic diversity, we added our institutional (UT Southwestern) EOCRC data given enrichment in Hispanic patients. Patients were divided into 4 racial/ethnic groups: White-Hispanic, White Non-Hispanic, Asian, Black. Using the Fisher Exact test (p&lt;0.05), we assessed differences in mutation frequency of actionable genes in CRC: KRAS, BRAFV600E, NRAS, ERBB2 amplification, MLH1, PMS2, MSH2, and MSH6. The Benjamini-Hochberg method was used to control for false discovery rate (q-value 0.2).Results: Among 1,105 EOCRC patients, 71 (6%) were Black, 80 (7%) White Hispanic (n=36 UTSW), 81 (7%) Asian, 873 (79%) White Non-Hispanic. 803 (73%) had primary lesions sampled, and 811 (73%) from colon. Mutations in MLH1, MSH2 or MSH6 were more common in primary tumors (MLH1 4.7% vs. 1.7%, p=0.021; MSH2 5.2% vs 1.7%, p=0.011; MSH6 6.1% vs 2.4% p=0.013) and BRAF mutations more common in colon cancers (5.9% colon vs. 1.0% rectum, p&lt;0.001). Notably, Black patients had higher rates of KRAS mutation (60.6%, p=0.004) and White Hispanic patients had higher rates of PMS2 mutation (6.3%, p=0.017). There were no other significant differences between race/ethnicity (Table 1).Conclusion: Our study identified differences in rates of KRAS and PMS2 mutations by race/ethnicity in EOCRC with enrichment of mutations among minority populations. Further research is needed to assess potential predictive and prognostic value of these findings.

Table 1.Distribution of mutations among racial groupsKRASWild TypeMutated% MutatedMLH1Wild TypeMutated% MutatedAsian522935.8%Asian7744.9%Black284360.6%*Black6834.2%White Hispanic512936.3%White Hispanic7378.8%White Non-Hispanic49038343.9%White Non-Hispanic844293.3%BRAF V600EWild TypeMutated% MutatedPMS2Wild TypeMutated% MutatedAsian7744.9%Asian7922.5%Black7011.4%Black6922.8%White Hispanic7911.3%White Hispanic7556.3%*White Non-Hispanic828455.2%White Non-Hispanic860131.5%NRASWild TypeMutated% MutatedMSH2Wild TypeMutated% MutatedAsian7833.7%Asian7922.5%Black6657.0%Black6834.2%White Hispanic7545.1%White Hispanic7733.8%White Non-Hispanic839354.0%White Non-Hispanic833404.6%ERBB2 (cna)Not amplified^1Amplified^2% AmplifiedMSH6Wild TypeMutated% MutatedAsian7833.7%Asian7833.7%Black6745.6%Black6657.0%White Hispanic7456.3%White Hispanic7378.8%White Non-Hispanic821536.1%White Non-Hispanic832414.7%*Significant with Benjamini-Hochberg, FDR=0.2, 48 tests^1 includes deletions^2 includes shallow amplification

Citation Format: David M. Hein, Weiye Deng, Syed A. Kazmi, Amy L. Jones, Radhika Kainthla, Brandi Cantarel, Nina N. Sanford. Racial and ethnic differences in genomic profiling of early onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 104.