Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer

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Drew, David A.Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States (författare)

Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer

Artikel/kapitelEngelska2024

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American Association for the Advancement of Science (AAAS),2024
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LIBRIS-ID:oai:DiVA.org:umu-225944
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225944URI
https://doi.org/10.1126/sciadv.adk3121DOI

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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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Kim, Andre E.Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Lin, YiPublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Qu, ConghuiPublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Morrison, JohnDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Lewinger, Juan PabloDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Kawaguchi, EricDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Wang, JunDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Fu, YuboDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Zemlianskaia, NataliaDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Díez-Obrero, VirginiaColorectal 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 (författare)
Bien, Stephanie A.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Dimou, NikiNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Albanes, DemetriusDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Baurley, James W.Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia (författare)
Wu, Anna H.Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Buchanan, Daniel D.Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, Parkville, United States; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, United States; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Parkville, Australia (författare)
Potter, John D.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand (författare)
Prentice, Ross L.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Harlid, Sophia,1978-Umeå universitet,Onkologi(Swepub:umu)soha0105 (författare)
Arndt, VolkerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (författare)
Barry, Elizabeth L.Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA (författare)
Berndt, Sonja I.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Bouras, EmmanouilLaboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece (författare)
Brenner, HermannDivision 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 (författare)
Budiarto, ArifBioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia (författare)
Burnett-Hartman, AndreaInstitute for Health Research, Kaiser Permanente Colorado, CO, Denver, United States (författare)
Campbell, Peter T.Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States (författare)
Carreras-Torres, RobertColorectal 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 (författare)
Casey, GrahamCenter for Public Health Genomics, University of Virginia, VA, Charlottesville, United States (författare)
Chang-Claude, JennyDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany (författare)
Conti, David V.Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Devall, Matthew A MDepartment of Family Medicine, University of Virginia, VA, Charlottesville, United States (författare)
Figueiredo, Jane C.Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States (författare)
Gruber, Stephen B.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 (författare)
Gsur, AndreaCenter for Cancer Research, Medical University Vienna, Vienna, Austria (författare)
Gunter, Marc J.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, United Kingdom (författare)
Harrison, Tabitha A.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Hidaka, AkihisaPublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Hoffmeister, MichaelDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (författare)
Huyghe, Jeroen R.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States (författare)
Jenkins, Mark A.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia (författare)
Jordahl, Kristina M.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, School of Public Health, University of Washington, WA, Seattle, United States (författare)
Kundaje, AnshulDepartment of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States (författare)
Le Marchand, LoicUniversity of Hawaii Cancer Center, HI, Honolulu, United States (författare)
Li, LiDepartment of Family Medicine, University of Virginia, VA, Charlottesville, United States; UVA Comprehensive Cancer Center, VA, Charlottesville, United States (författare)
Lynch, Brigid M.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia (författare)
Murphy, NeilNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Nassir, RamiDepartment of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia (författare)
Newcomb, Polly A.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States (författare)
Newton, Christina C.Department of Population Science, American Cancer Society, GA, Atlanta, United States (författare)
Obón-Santacana, MireiaColorectal 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, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain (författare)
Ogino, ShujiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States; Broad Institute of MIT and Harvard, MA, Cambridge, United States (författare)
Ose, JenniferHuntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States (författare)
Pai, Rish K.Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States (författare)
Palmer, Julie R.Slone Epidemiology Center at Boston University, MA, Boston, United States (författare)
Papadimitriou, NikosNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Pardamean, BensBioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia (författare)
Pellatt, Andrew J.Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, TX, Houston, United States (författare)
Peoples, Anita R.Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States (författare)
Platz, Elizabeth A.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States (författare)
Rennert, GadDepartment 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 (författare)
Ruiz-Narvaez, EdwardDepartment of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States (författare)
Sakoda, Lori C.Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States (författare)
Scacheri, Peter C.Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States (författare)
Schmit, Stephanie L.Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, OH, Cleveland, United States (författare)
Schoen, Robert E.Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States (författare)
Stern, Mariana C.Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Su, Yu-RuBiostatistics Division, Kaiser Permanente Washington Health Research Institute, WA, Seattle, United States (författare)
Thomas, Duncan C.Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Tian, YuDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China (författare)
Tsilidis, Konstantinos K.Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (författare)
Ulrich, Cornelia M.Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States (författare)
Um, Caroline Y.Department of Population Science, American Cancer Society, GA, Atlanta, United States (författare)
van Duijnhoven, Fränzel J BDivision of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands (författare)
van Guelpen, BethanyUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi(Swepub:umu)beyvan99 (författare)
White, EmilyPublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, School of Public Health, University of Washington, WA, Seattle, United States (författare)
Hsu, LiPublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States (författare)
Moreno, VictorColorectal 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, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 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, Barcelona, Spain (författare)
Peters, UlrikePublic Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, School of Public Health, University of Washington, WA, Seattle, United States (författare)
Chan, Andrew T.Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States (författare)
Gauderman, W JamesDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United StatesDivision of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (creator_code:org_t)

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Ingår i:Science Advances: American Association for the Advancement of Science (AAAS)10:222375-2548

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Av författaren/redakt...: Drew, David A.; Kim, Andre E.; Lin, Yi; Qu, Conghui; Morrison, John; Lewinger, Juan P ...; visa fler...; Kawaguchi, Eric; Wang, Jun; Fu, Yubo; Zemlianskaia, Na ...; Díez-Obrero, Vir ...; Bien, Stephanie ...; Dimou, Niki; Albanes, Demetri ...; Baurley, James W ...; Wu, Anna H.; Buchanan, Daniel ...; Potter, John D.; Prentice, Ross L ...; Harlid, Sophia, ...; Arndt, Volker; Barry, Elizabeth ...; Berndt, Sonja I.; Bouras, Emmanoui ...; Brenner, Hermann; Budiarto, Arif; Burnett-Hartman, ...; Campbell, Peter ...; Carreras-Torres, ...; Casey, Graham; Chang-Claude, Je ...; Conti, David V.; Devall, Matthew ...; Figueiredo, Jane ...; Gruber, Stephen ...; Gsur, Andrea; Gunter, Marc J.; Harrison, Tabith ...; Hidaka, Akihisa; Hoffmeister, Mic ...; Huyghe, Jeroen R ...; Jenkins, Mark A.; Jordahl, Kristin ...; Kundaje, Anshul; Le Marchand, Loi ...; Li, Li; Lynch, Brigid M.; Murphy, Neil; Nassir, Rami; Newcomb, Polly A ...; Newton, Christin ...; Obón-Santacana, ...; Ogino, Shuji; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, N ...; Pardamean, Bens; Pellatt, Andrew ...; Peoples, Anita R ...; Platz, Elizabeth ...; Rennert, Gad; Ruiz-Narvaez, Ed ...; Sakoda, Lori C.; Scacheri, Peter ...; Schmit, Stephani ...; Schoen, Robert E ...; Stern, Mariana C ...; Su, Yu-Ru; Thomas, Duncan C ...; Tian, Yu; Tsilidis, Konsta ...; Ulrich, Cornelia ...; Um, Caroline Y.; van Duijnhoven, ...; van Guelpen, Bet ...; White, Emily; Hsu, Li; Moreno, Victor; Peters, Ulrike; Chan, Andrew T.; Gauderman, W Jam ...; visa färre...

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