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Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.
Drew, David A; Kim, Andre E; Lin, Yi; Qu, Conghui; Morrison, John; Lewinger, Juan Pablo; Kawaguchi, Eric; Wang, Jun; Fu, Yubo; Zemlianskaia, Natalia; Díez-Obrero, Virginia; Bien, Stephanie A; Dimou, Niki; Albanes, Demetrius; Baurley, James W; Wu, Anna H; Buchanan, Daniel D; Potter, John D; Prentice, Ross L; Harlid, Sophia; Arndt, Volker; Barry, Elizabeth L; Berndt, Sonja I; Bouras, Emmanouil; Brenner, Hermann; Budiarto, Arif; Burnett-Hartman, Andrea; Campbell, Peter T; Carreras-Torres, Robert; Casey, Graham; Chang-Claude, Jenny; Conti, David V; Devall, Matthew A M; Figueiredo, Jane C; Gruber, Stephen B; Gsur, Andrea; Gunter, Marc J; Harrison, Tabitha A; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R; Jenkins, Mark A; Jordahl, Kristina M; Kundaje, Anshul; Le Marchand, Loic; Li, Li; Lynch, Brigid M; Murphy, Neil; Nassir, Rami; Newcomb, Polly A.
Afiliação
  • Drew DA; Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Kim AE; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Lin Y; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
  • Morrison J; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
  • Lewinger JP; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kawaguchi E; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Wang J; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Fu Y; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Zemlianskaia N; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Díez-Obrero V; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bien SA; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Dimou N; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
  • Albanes D; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
  • Baurley JW; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
  • Wu AH; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Buchanan DD; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Potter JD; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Prentice RL; BioRealm LLC, Walnut, CA, USA.
  • Harlid S; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Arndt V; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria 3010 Australia.
  • Barry EL; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria 3010 Australia.
  • Berndt SI; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Bouras E; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
  • Brenner H; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
  • Budiarto A; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
  • Burnett-Hartman A; Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
  • Campbell PT; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Carreras-Torres R; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • Casey G; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chang-Claude J; Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Conti DV; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Devall MAM; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Figueiredo JC; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gruber SB; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Gsur A; Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
  • Gunter MJ; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Harrison TA; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Hidaka A; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190 Girona, Spain.
  • Hoffmeister M; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Huyghe JR; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jenkins MA; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Jordahl KM; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kundaje A; Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
  • Le Marchand L; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Li L; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lynch BM; Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
  • Murphy N; Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
  • Nassir R; Center for Cancer Research, Medical University Vienna, Vienna, Austria.
  • Newcomb PA; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Sci Adv ; 10(22): eadk3121, 2024 May 31.
Article em En | MEDLINE | ID: mdl-38809988
ABSTRACT
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Anti-Inflamatórios não Esteroides / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Anti-Inflamatórios não Esteroides / Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article