DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations

Authors: LI, JASON SHENG - University Of California Irvine; RIGGINS, KAREN - Children'S Nutrition Research Center (CNRC); YANG, LI - Children'S Nutrition Research Center (CNRC); CHEN, CHAORONG - University Of California Irvine; CASTRO, PATRICIA - Baylor College Of Medicine; ALFARKH, WEDAD - Baylor College Of Medicine; ZARRIN-KHAMEH, NEDA - Baylor College Of Medicine; SCHEURER, MICHAEL - Baylor College Of Medicine; CREIGHTON, CHAD - Baylor College Of Medicine; MUSHER, BENJAMIN - Baylor College Of Medicine; LI, WEI - University Of California Irvine; SHEN, LANLAN - Children'S Nutrition Research Center (CNRC)

Submitted to: Clinical Epigenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2025
Publication Date: 1/22/2025
Citation: Li, J., Riggins, K., Yang, L., Chen, C., Castro, P., Alfarkh, W., Zarrin-Khameh, N., Scheurer, M.E., Creighton, C.J., Musher, B., Li, W., Shen, L. 2025. DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations. Clinical Epigenetics. https://doi.org/10.1186/s13148-025-01817-z.
DOI: https://doi.org/10.1186/s13148-025-01817-z

Interpretive Summary: This study examines early-onset colorectal cancer (EOCRC), which is becoming more common in the U.S., especially among susceptible patients from Texas. Researchers analyzed the DNA of these patients and found that their genes were marked differently compared to older colorectal cancer patients. They discovered DNA changes, called methylation, in tumor tissue that affected genes linked to cancer growth. The study also found unique changes in genes related to metabolism that were specific to the Texas cohort, such as MFAP2, which helps protect against obesity, and genes like APOL3 and RNASEL, linked to cancer risk. This research helps us better understand EOCRC in susceptible patients and suggests that these DNA changes could be used to improve diagnosis and treatment. It also highlights the importance of metabolism-related genes in cancer, showing how diet and lifestyle could influence these genes and help create better strategies to prevent cancer, especially in high-risk populations.

Technical Abstract: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, disproportionately affecting certain patient groups. In this study, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Texas patients susceptible to the disease. We demonstrate that the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients. Methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Additionally, we identify epigenetic alterations in metabolic genes that are specific to our cohort but not observed in Caucasian patients from TCGA. Top genes differentially methylated between these cohorts include the obesity-protective MFAP2 gene, as well as cancer risk susceptibility genes APOL3 and RNASEL. In summary, we provide the scientific community with high-resolution DNA methylomes from a unique cohort of EOCRC patients. Our exploratory findings highlight key epigenetic mechanisms underlying the pathogenesis of EOCRC and suggest novel biomarkers for EOCRC in these populations.