Association of germline variants with KRAS-mutation status in colorectal cancer

Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or alteri...

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Detalles Bibliográficos
Autores: Tjader, Nijole Pollock, Ramroop, Johnny, Gandhi, Tanish, Dauch, Cara, Meadows, Owen, Stevens, Patrick, Pearlman, Rachel, Hampel, Heather, Aglago, Elom K., Berndt, Sonja I., Bloomer, Amanda, Brenner, Hermann, Buchanan, Daniel D, Campbell, Peter T., Cao, Yin, Chan, Andrew T., Cheng, Iona, Dimou, Niki, Drew, David A., French, Amy J., Georgeson, Peter, Giannakis, Marios, Giles, Graham G., Gomez, Maria, Gruber, Stephen B., Hoffmeister, Michael, Huang, Wen-Yi, Hullar, Meredith Aj., Huyghe, Jeroen R., Loroña, Nicole, Moreno Aguado, Víctor, Newton, Christina C., Nowak, Jonathan A., Obón Santacana, Mireia, Ogino, Shuji, Pellatt, Andrew J., Peoples, Anita R., Permuth, Jennifer B., Schmit, Stephanie L., Schoen, Robert E., Siegel, Erin M., Steinfelder, Robert, Sun, Wei, Teer, Jamie K., Thomas, Claire E., Trinh, Quang M., Tsilidis, Konstantinos K., Ugai, Tomotaka, Um, Caroline Y., Van Guelpen, Bethany, Zaidi, Syed H., Figueiredo, Jane C., Peters, Ulrike, Phipps, Amanda I., McElroy, Joseph Paul, Toland, Amanda E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:dnet:recercat____::a777a6df1a2d514669a633049349e275
Acceso en línea:https://hdl.handle.net/2445/229630
Access Level:acceso abierto
Palabra clave:Carcinogènesi
Càncer colorectal
Carcinogenesis
Colorectal cancer
Descripción
Sumario:Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or altering cellular, immunological and/or microenvironmental responses after a mutation. We hypothesized that the germline genetic background modifies somatic KRAS mutation frequency in CRC. To test this, we performed a genome-wide association study (GWAS) in 7071 individuals with CRC, using KRAS mutation status as the phenotype. Single-nucleotide variants were chosen for validation analyses based on P values from the discovery GWAS, predicted in silico functional effects, and proximity to genes with potential cancer relevance. A validation analysis of 101 SNVs of interest was performed in 2482 individuals. No SNVs were significantly associated with KRAS-mutant CRC (P value < 0.0005). One variant rs73067863-T showed a non-significant exploratory association with fewer KRAS-mutant tumors in the combined sample (P value = 9.7 × 10–7, OR = 0.75). Follow-up studies are needed to determine if these or other germline variants impact population differences in KRAS mutations in CRC.

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