ArticleScientific reports2026
Association of germline variants with KRAS-mutation status in colorectal cancer.
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Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1citing papers in PubMed
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1 citing paper in PubMed.
- Mutations of Kinases and GTPases in Cancers.Cancers · 2026Article
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Authors and funding
56 authors.
Nijole Pollock TjaderDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 460 West 12th Avenue, Biomedical Research Tower Room 998, Columbus, OH, 43210, USA.
Johnny RamroopBiology Department, The City College of New York, The City University of New York, New York, NY, USA.
Tanish GandhiCollege of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Cara DauchDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 460 West 12th Avenue, Biomedical Research Tower Room 998, Columbus, OH, 43210, USA.
Owen MeadowsDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 460 West 12th Avenue, Biomedical Research Tower Room 998, Columbus, OH, 43210, USA.
Patrick StevensDepartment of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Rachel PearlmanDivision of Human Genetics, Department of Internal Medicine, Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Heather HampelDivision of Clinical Cancer Genomics, City of Hope National Medical Center, Duarte, CA, USA.
Elom K AglagoDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Amanda BloomerDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniel D BuchananColorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
Peter T CampbellDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Yin CaoDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Andrew T ChanChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Iona ChengDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Niki DimouSection of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
David A DrewClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Amy J FrenchDivision of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Peter GeorgesonColorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Graham G GilesCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Maria GomezDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Stephen B GruberDepartment of Medical Oncology and Therapeutics Research and Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Meredith A J HullarPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Jeroen R HuyghePublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nicole LoroñaSamuel Oschin Comprehensive Cancer Institute at Cedars Sinai Medical Center, Los Angeles, CA, USA.
Victor MorenoUnit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, 08908, Barcelona, Spain.
Christina C NewtonDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Jonathan A NowakProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Mireia Obón-SantacanaUnit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, 08908, Barcelona, Spain.
Shuji OginoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Andrew PellattDepartment of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Anita R PeoplesDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Jennifer B PermuthDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Stephanie L SchmitGenomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Erin M SiegelDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Robert S SteinfelderPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Wei SunPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Jamie K TeerDepartment of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA.
Claire E ThomasPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Quang M TrinhOntario Institute for Cancer Research, Toronto, ON, Canada.
Konstantinos TsilidisDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Tomotaka UgaiProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Caroline Y UmDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Bethany Van GuelpenDepartment of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden.
Syed H ZaidiOntario Institute for Cancer Research, Toronto, ON, Canada.
Jane FigueiredoDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute at Cedars Sinai Medical Center, Los Angeles, CA, USA.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Amanda I PhippsPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Joseph Paul McElroyCenter for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Amanda Ewart TolandDepartment of Cancer Biology and Genetics, Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center, 460 West 12th Avenue, Biomedical Research Tower Room 998, Columbus, OH, 43210, USA. Amanda.toland@osumc.edu.
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MTranslational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MTranslational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3MTRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5MStatistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FUCHS, CHARLES S · 1991 to 2009
$41.8MLife Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MCancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0MData sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8MSEATTLE FAMILIAL COLORECTAL CANCER REGISTRYU01CA074794 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEWCOMB, POLLY A · 1997 to 2007
$14.1MAmerican Cancer Society CRP-24-1185864-01-PROFAmerican Institute for Cancer Research Investigator Initiated GrantBrigham and Women's Hospital Faculty Career Development AwardNCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA015704NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA155101NCI NIH HHS R01 CA176272NCI NIH HHS R01 CA215151NCI NIH HHS R01 CA248857NCI NIH HHS R35 CA197735NCI NIH HHS R35 CA253185NCI NIH HHS R50 CA274122NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA152753NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS U19 CA148107NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107NHGRI NIH HHS U54 HG003067NIH HHS R01 CA155101NIH HHS R01 CA248857NIH HHS R01 CA81488NIH HHS R50 CA274122Pelotonia Pelotonia Graduate Research FellowshipPelotonia Pelotonia Postdoctoral FellowshipPelotonia Undergraduate Research Fellowship
Abstract
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
Indexed as
Colorectal NeoplasmsGerm-Line MutationProto-Oncogene Proteins p21(ras)AgedFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideKRAS protein, humanProto-Oncogene Proteins p21(ras)Colorectal cancerGermline variantsGWASKRASSomatic mutations
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