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https://repository.monashhealth.org/monashhealthjspui/handle/1/27311| Title: | A transcriptome-wide association study identifies novel candidate susceptibility genes for pancreatic cancer. | Authors: | Hasan M.;Zhang T.;Xiao W.;Albanes D.;Andreotti G.;Arslan A.A.;Babic A.;Bamlet W.R.;Beane-Freeman L.;Berndt S.;Borgida A.;Bracci P.M.;Brais L.;Brennan P.;Bueno-De-Mesquita B.;Buring J.;Canzian F.;Childs E.J.;Cotterchio M.;Du M.;Duell E.J.;Fuchs C.;Gallinger S.;Michael Gaziano J.;Giles G.G.;Giovannucci E.;Goggins M.;Goodman G.E.;Goodman P.J.;Haiman C.;Hartge P.;Helzlsouer K.J.;Holly E.A.;Klein E.A.;Kogevinas M.;Kurtz R.J.;LeMarchand L.;Malats N.;Mannisto S.;Milne R.;Neale R.E.;Ng K.;Obazee O.;Oberg A.L.;Orlow I.;Patel A.V.;Peters U.;Porta M.;Rothman N.;Scelo G.;Sesso H.D.;Severi G.;Sieri S.;Silverman D.;Sund M.;Tjonneland A.;Thornquist M.D.;Tobias G.S.;Trichopoulou A.;van Den Eeden S.K.;Visvanathan K.;Wactawski-Wende J.;Wentzensen N.;White E.;Yu H.;Yuan C.;Zeleniuch-Jacquotte A.;Hoover R.;Brown K.;Kooperberg C.;Risch H.A.;Jacobs E.J.;Li D.;Yu K.;Shu X.-O.;Chanock S.J.;Wolpin B.M.;Stolzenberg-Solomon R.Z.;Chatterjee N.;Klein A.P.;Smith J.P.;Kraft P.;Shi J.;Petersen G.M.;Zheng W.;Amundadottir L.T.;Zhong J.;Jermusyk A.;Wu L.;Hoskins J.W.;Collins I.;Mocci E.;Zhang M.;Song L.;Chung C.C. | Institution: | (Zhong, Jermusyk, Hoskins, Collins, Zhang, Brown, Amundadottir) Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States (Wu, Shu, Zheng) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States (Mocci, Childs, Klein) Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States (Zhang) US Food and Drug Administration, Silver Spring, MD, United States (Song, Chung, Zhang, Albanes, Andreotti, Beane-Freeman, Berndt, Hartge, Rothman, Silverman, Tobias, Wentzensen, Hoover, Yu, Chanock, Stolzenberg-Solomon, Chatterjee, Shi) Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States (Xiao) National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, United States (Xiao) Division of Molecular Genetics and Pathology, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, United States (Arslan) Department of Obstetrics and Gynecology, New York University, School of Medicine, New York, NY, United States (Arslan, Zeleniuch-Jacquotte) Department of Population Health, New York University, School of Medicine, New York, NY, United States (Arslan) Department of Environmental Medicine, New York University, School of Medicine, New York, NY, United States (Babic, Brais, Giovannucci, Ng, Yuan, Wolpin) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States (Bamlet, Oberg, Petersen) Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States (Borgida, Gallinger) Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada (Bracci) Department of Epidemiology and Biostatistics, University of California, CA, United States (Brennan, Scelo) International Agency for Research on Cancer, Lyon, France (Bueno-De-Mesquita) Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, BA, Bilthoven, Netherlands (Bueno-De-Mesquita) Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands (Bueno-De-Mesquita) Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom (Bueno-De-Mesquita) Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (Buring, Michael Gaziano, Sesso) Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, United States (Buring, Sesso, Kraft) Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States (Canzian, Obazee) Genomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany (Cotterchio) Cancer Care Ontario, University of Toronto, Toronto, ON, Canada (Cotterchio) Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada (Du, Orlow) Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States (Duell) Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology, Barcelona, Spain (Fuchs) Yale Cancer Center, New Haven, CT, United States (Michael Gaziano) Division of Aging, Brigham and Women's Hospital, Boston, MA, United States (Michael Gaziano) Boston VA Healthcare System, Boston, MA, United States (Giles, Milne, Scelo) Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia (Giles, Milne, Scelo) Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia (Giles) Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia (Goggins, Klein) Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, United States (Goodman, Peters, Thornquist, White, Kooperberg) Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (Goodman) SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (Haiman) Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States (Hasan) Department of Epidemiology, University of Texas, MD Anderson Cancer Center, Houston, TX, United States (Helzlsouer) Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States (Holly) Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States (Klein) Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, United States (Kogevinas) ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain (Kogevinas, Porta) CIBER Epidemiologia y Salud Publica, Barcelona, Spain (Kogevinas, Porta) Hospital del Mar Institute of Medical Research, Universitat Autonoma de Barcelona, Barcelona, Spain (Kogevinas) Universitat Pompeu Fabra, Barcelona, Spain (Kurtz) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States (LeMarchand, Yu) Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States (Malats) Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain (Mannisto) Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland (Milne) Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia (Neale) Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia (Patel) Epidemiology Research Program, American Cancer Society, Atlanta, GA, United States (Severi) Centre de Recherche en Epidemiologie et Sante des Populations, CESP, Inserm U1018, Facultes de Medicine, Universite Paris-Saclay, UPS, UVSQ, Gustave Roussy, Villejuif, France (Sieri) Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy (Sund) Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden (Tjonneland) Danish Cancer Society Research Center, Copenhagen, Denmark (Tjonneland) Department of Public Health, University of Copenhagen, Copenhagen, Denmark (Tjonneland) Hellenic Health Foundation, Athens, Greece (van Den Eeden) Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States (Visvanathan) Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States (Wactawski-Wende) Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, United States (White) Department of Epidemiology, University of Washington, Seattle, WA, United States (Zeleniuch-Jacquotte) Perlmutter Cancer Center, New York University, School of Medicine, New York, NY, United States (Risch) Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, United States (Jacobs) Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, United States (Li) Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, United States (Chatterjee) Department of Biostatistics, Bloomberg School of Public Health, Baltimore, MD, United States (Smith) Department of Medicine, Georgetown University, Washington, DC, United States (Kraft) Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States | Issue Date: | 12-Feb-2021 | Copyright year: | 2020 | Publisher: | Oxford University Press | Place of publication: | United Kingdom | Publication information: | Journal of the National Cancer Institute. 112 (10) (pp 1003-1012), 2020. Date of Publication: 01 Oct 2020. | Journal: | Journal of the National Cancer Institute | Abstract: | Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Method(s): To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Result(s): We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate <.05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22:RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusion(s): By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.Copyright © 2020 Oxford University Press. All rights reserved. | DOI: | http://monash.idm.oclc.org/login?url= http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1093/jnci/djz246 |
PubMed URL: | 31917448 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31917448] | ISSN: | 0027-8874 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/27311 | Type: | Article |
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