Year: 2026
Type: preprint
Study design: Observational Study
Abstract: ABSTRACT PURPOSE Colorectal cancer (CRC) incidence and mortality rates differ by population, and evidence suggests that genetic differences may affect cancer biology. However, studies investigating CRC variants in genetically heterogeneous populations are limited. Using somatic tumor mutation profiling of CRCs diagnosed in African Americans (AAs), Ghanaians, Ethiopians, and NHWs, we explore correlations between population group and population-specific tumor variants. PATIENTS AND METHODS Somatic DNA from CRC tumors resected from 150 individuals, including 43 AAs (27%), 53 NHWs (35%), 21 Ghanaians (14.2%), and 33 Ethiopians (22.3%), was sequenced on the Illumina NovaSeq platform, targeting 290 genes. We compared mutations in AAs, Ghanaians, and Ethiopians to those in NHWs to identify variants enriched in historically underrepresented groups. RESULTS US cohort tumors were diagnosed at significantly younger ages with more early-onset cases (<50 years old) than African cohorts ( p <0.05). Significant differences were observed in primary tumor location, MMR phenotypes, KRAS mutations, and distribution of tumor mutational burden by population. BRAF V600E mutations were rare across all groups, while non- V600E BRAF mutation rates were higher in AA and NHW (43-44%) than Ethiopian and Ghanaian (14-33%) samples. Population-specific differences were identified in mutation rates of APC, CTNNB1, RNF43, PIK3CA, and TP53 , as well as in pathogenic variant occurrence. CONCLUSION Geographic origin and age of onset appear to shape the CRC mutational landscape. The similarity between AA and NHW tumor profiles likely reflects their shared predominance of early-onset cases, suggesting that age- and geography-associated factors, including environmental exposures, may influence tumor phenotypes.
Source: medRxiv
Authors: Batsirai M. Mabvakure, Patharapa Promprasert, Lucia Martinez Cruz, Siddhi Patil, John Barros, Matthew Hayhurst, Elham Mohebbi, Deborah de la Caridad Delgado Herrera, Grace Lee, Sophia Latif, Fiona Williams, Rashmi Samdani, Anju Duttargi, Bereket Berhane, Esmael Besufikad, Selamawit Tadesse, Aisha Jibril Suleiman, Christina Lefante, Mei-Chin Hsieh, Kristen Purrington, Ernest Adjei, Tingting Qin, Maureen Sartor, Elena M. Stoffel, Laura S. Rozek
Institutions: Georgetown University, University of the Witwatersrand, Georgetown Lombardi Comprehensive Cancer Center, St. Paul's Hospital Millennium Medical College, Louisiana State University Health Sciences Center New Orleans, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Komfo Anokye Teaching Hospital, University of Michigan, U-M Rogel Cancer Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7166551732