Abstract C057: Methylome-wide profiling of early-onset colorectal cancer in underrepresented populations

Abstract

Abstract Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women in the United States. Late onset colorectal cancer (LOCRC) or CRC diagnosed in older adults >50 years old has continued to decline while early onset colorectal cancer (EOCRC) or colorectal cancer in patients under the age of 50 continues to rise at an alarming rate since the mid-1990s. In fact, EOCRC is now the second most common cancer and the third leading cause of cancer mortality in people <50 years of age in the USA. The incidence of EOCRC has been on the rise over the past four decades and is expected to increase by >140% by 2030. Notably, Blacks and Hispanics are disproportionately affected with the EOCRC diagnosis. Despite this, minority patients remain underrepresented in clinical trials and translational research. It has been proposed that environmental exposures including westernized diet, metabolic factors, and the microbiome might be responsible for the rise in incidence of EOCRC. Epigenetic modifications are well-known mechanisms by which the environment can modulate gene expression without changing the DNA sequence. One such modification is DNA methylation, which controls DNA accessibility, chromatin formation, and gene transcriptional activity. Unfortunately, however, little is known about the role of DNA methylation in EOCRC and much less is understood of EOCRC in minority populations. Therefore, we identified a unique cohort of 11 EOCRC patients within the Baylor College of Medicine/Harris Health System which is comprised of majority minority EOCRC population (7- Hispanic, 2 Non-Hispanic (NH) Black, and 1 NH-White EOCRC patients). Using whole-genome bisulfite sequencing, we comprehensively characterized the DNA methylome at single-base resolution in our 11 EOCRC patient samples. Our analyses revealed distinct EOCRC methylation patterns including both global hypomethylation and promoter-specific hypermethylation, which were not previously captured in The Cancer Genome Atlas (TCGA) Analyses. Among the differentially methylated regions (DMRs), we discovered that DNA and RNA transcription pathways were enriched in EOCRCs at advanced stage. Furthermore, we identify differential DMRs patterns among ethnicities. Taken together, our work supports a pathogenic role for DNA methylation in EOCRC. We are the first group to take this comprehensive unbiased approach to analyze the methylome in an underrepresented EOCRC cohort of patients. Citation Format: Karen Riggins, Jason Sheng Li, Benjamin Musher, Li Yang, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Kamah, Michael Scheurer, Chad Creighton, Wei Li, Lanlan Shen. Methylome-wide profiling of early-onset colorectal cancer in underrepresented populations [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 C057.