دورية أكاديمية
Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer.
العنوان: | Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer. |
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المؤلفون: | Drew DA; Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Kim AE; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Lin Y; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Morrison J; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 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; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Fu Y; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 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; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain., Bien SA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Dimou N; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Albanes D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Baurley JW; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.; BioRealm LLC, Walnut, CA, USA., Wu AH; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Buchanan DD; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria 3010 Australia.; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria 3010 Australia.; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia., Potter JD; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand., Prentice RL; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Harlid S; Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden., Arndt V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Barry EL; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Bouras E; Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Budiarto A; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia., Burnett-Hartman A; Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA., Campbell PT; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Carreras-Torres R; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190 Girona, Spain., Casey G; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany., Conti DV; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Devall MAM; Department of Family Medicine, University of Virginia, Charlottesville, VA, USA., Figueiredo JC; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Gruber SB; Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.; Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA., Gsur A; Center for Cancer Research, Medical University Vienna, Vienna, Austria., Gunter MJ; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK., Harrison TA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Hidaka A; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Hoffmeister M; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Huyghe JR; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Jenkins MA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia., Jordahl KM; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA., Kundaje A; Department of Genetics, Stanford University, Stanford, CA, USA.; Department of Computer Science, Stanford University, Stanford, CA, USA., Le Marchand L; University of Hawaii Cancer Center, Honolulu, HI, USA., Li L; Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.; UVA Comprehensive Cancer Center, Charlottesville, VA, USA., Lynch BM; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia., Murphy N; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Nassir R; Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia., Newcomb PA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; School of Public Health, University of Washington, Seattle, WA, USA., Newton CC; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Obón-Santacana M; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, 08908 Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain., Ogino S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ose J; Huntsman Cancer Institute, Salt Lake City, UT, USA.; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA., Pai RK; Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA., Palmer JR; Slone Epidemiology Center at Boston University, Boston, MA, USA., Papadimitriou N; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Pardamean B; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia., Pellatt AJ; Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Peoples AR; Huntsman Cancer Institute, Salt Lake City, UT, USA.; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA., Platz EA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Rennert G; Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Clalit National Cancer Control Center, Haifa, Israel., Ruiz-Narvaez E; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA., Sakoda LC; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Scacheri PC; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA., Schmit SL; Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA., Schoen RE; Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Stern MC; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Su YR; Biostatistics Division, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA., Thomas DC; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Tian Y; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; School of Public Health, Capital Medical University, Beijing, China., Tsilidis KK; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK.; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Ulrich CM; Huntsman Cancer Institute, Salt Lake City, UT, USA.; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA., Um CY; Department of Population Science, American Cancer Society, Atlanta, GA, USA., van Duijnhoven FJB; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands., Van Guelpen B; Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden., White E; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA., Hsu L; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Biostatistics, University of Washington, Seattle, WA, USA., Moreno V; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, 08908 Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain.; Department of Clinical Sciences, Faculty of Medicine and Health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Peters U; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA., Chan AT; Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA., Gauderman WJ; Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. |
المصدر: | Science advances [Sci Adv] 2024 May 31; Vol. 10 (22), pp. eadk3121. Date of Electronic Publication: 2024 May 29. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
مواضيع طبية MeSH: | Colorectal Neoplasms*/genetics , Colorectal Neoplasms*/drug therapy , Anti-Inflammatory Agents, Non-Steroidal*/pharmacology , Genome-Wide Association Study* , Polymorphism, Single Nucleotide*, Humans ; Aspirin/pharmacology ; Receptors, Prostaglandin E, EP4 Subtype/genetics ; Receptors, Prostaglandin E, EP4 Subtype/metabolism ; Male ; Genetic Predisposition to Disease ; Female ; Case-Control Studies ; Middle Aged ; Genetic Loci ; Aged |
مستخلص: | 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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معلومات مُعتمدة: | 001 International WHO_ World Health Organization; K01 DK120742 United States DK NIDDK NIH HHS; P01 CA196569 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Anti-Inflammatory Agents, Non-Steroidal) R16CO5Y76E (Aspirin) 0 (Receptors, Prostaglandin E, EP4 Subtype) 0 (PTGER4 protein, human) |
تواريخ الأحداث: | Date Created: 20240529 Date Completed: 20240529 Latest Revision: 20240730 |
رمز التحديث: | 20240730 |
مُعرف محوري في PubMed: | PMC11135391 |
DOI: | 10.1126/sciadv.adk3121 |
PMID: | 38809988 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2375-2548 |
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DOI: | 10.1126/sciadv.adk3121 |