Journal article
Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
Nature genetics, Vol.46(11), pp.1233-1238
11/2014
DOI: 10.1038/ng.3105
PMCID: PMC4213349
PMID: 25261932
Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
Details
- Title: Subtitle
- Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
- Creators
- James R Cerhan - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USASonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USABrian K Link - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USAGeorge J Weiner - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USAJoseph Vijai - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USAHervé Ghesquières - 1] Department of Hematology, Centre Léon Bérard, Lyon, France. Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, CNRS, Pierre-Benite, FranceAhmet Dogan - Department of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USAJames McKay - Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon, FranceSophia S Wang - Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California, USAZhaoming Wang - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland, USAMeredith Yeager - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland, USALucia Conde - 1] Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, Alabama, USA. Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAPaul I W de Bakker - 1] Department of Medical Genetics and of Epidemiology, University Medical Center Utrecht, Utrecht, the Netherlands. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the NetherlandsAlexandra Nieters - Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, GermanyDavid Cox - Lyon, FranceLaurie Burdett - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland, USAAlain Monnereau - 1] Environmental Epidemiology of Cancer Group, INSERM, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. UMRS 1018, Université Paris Sud, Villejuif, France. Registre des Hémopathies Malignes de la Gironde, Institut Bergonié, Bordeaux, FranceQing Lan - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAChristopher R Flowers - Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USAGianluca Severi - 1] Human Genetics Foundation, Turin, Italy. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria, AustraliaAnneclaire J De Roos - 1] Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USAMads Melbye - 1] Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark. Department of Medicine, Stanford University School of Medicine, Stanford, California, USAAngela R Brooks-Wilson - 1] Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, CanadaJian Gu - Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, USARebecca D Jackson - Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, Ohio, USAEleanor Kane - Department of Health Sciences, University of York, York, UKLauren R Teras - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USAMark P Purdue - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAClaire M Vajdic - Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, AustraliaJohn J Spinelli - 1] Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada. School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, CanadaGraham G Giles - 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria, AustraliaDemetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USARachel S Kelly - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Medical Research Council (MRC)-Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UKMariagrazia Zucca - Department of Biomedical Science, University of Cagliari, Monserrato, ItalyKimberly A Bertrand - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USAAnne Zeleniuch-Jacquotte - 1] Department of Population Health, New York University School of Medicine, New York, New York, USA. Cancer Institute, New York University School of Medicine, New York, New York, USACharles Lawrence - Health Studies Sector, Westat, Rockville, Maryland, USAAmy Hutchinson - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland, USADegui Zhi - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USAThomas M Habermann - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAAnne J Novak - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAYan W Asmann - Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USAMark Liebow - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USACarrie A Thompson - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAStephen M Ansell - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAThomas E Witzig - Department of Medicine, Mayo Clinic, Rochester, Minnesota, USAAmelie S Veron - Lyon, FranceDiana Zelenika - Centre National de Génotypage, Evry, FranceHervé Tilly - Centre Heni Becquerel, Rouen, FranceCorinne Haioun - Department of Hematology, Centre Hospitalier Universitaire (CHU) Henri Mondor, Creteil, FranceThierry Jo Molina - Department of Pathology, Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceHenrik Hjalgrim - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, DenmarkBengt Glimelius - 1] Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, SwedenHans-Olov Adami - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenPaige M Bracci - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USAJacques Riby - 1] Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, Alabama, USA. Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAMartyn T Smith - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAElizabeth A Holly - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USAWendy Cozen - 1] Department of Preventive Medicine, University of Southern California Keck School of Medicine, University of Southern California, Los Angeles, California, USA. Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, University of Southern California, Los Angeles, California, USAPatricia Hartge - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USALindsay M Morton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USARichard K Severson - Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USALesley F Tinker - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USAKari E North - 1] Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USANikolaus Becker - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyYolanda Benavente - 1] Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainPaolo Boffetta - Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USAPaul Brennan - Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon, FranceLenka Foretova - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Masaryk University, Brno, Czech RepublicMarc Maynadie - Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, FranceAnthony Staines - School of Nursing and Human Sciences, Dublin City University, Dublin, IrelandTracy Lightfoot - Department of Health Sciences, University of York, York, UKSimon Crouch - Department of Health Sciences, University of York, York, UKAlex Smith - Department of Health Sciences, University of York, York, UKEve Roman - Department of Health Sciences, University of York, York, UKW Ryan Diver - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USAKenneth Offit - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USAAndrew Zelenetz - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USARobert J Klein - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USADanylo J Villano - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USATongzhang Zheng - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USAYawei Zhang - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USATheodore R Holford - Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USAAnne Kricker - Sydney School of Public Health, University of Sydney, Sydney, New South Wales, AustraliaJenny Turner - 1] Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia. Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, AustraliaMelissa C Southey - Department of Pathology, University of Melbourne, Parkville, Victoria, AustraliaJacqueline Clavel - 1] Environmental Epidemiology of Cancer Group, INSERM, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. UMRS 1018, Université Paris Sud, Villejuif, FranceJarmo Virtamo - Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, FinlandStephanie Weinstein - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAElio Riboli - School of Public Health, Imperial College London, London, UKPaolo Vineis - 1] Human Genetics Foundation, Turin, Italy. Medical Research Council (MRC)-Public Health England (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UKRudolph Kaaks - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyDimitrios Trichopoulos - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Hellenic Health Foundation, Athens, GreeceRoel C H Vermeulen - 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the NetherlandsHeiner Boeing - Department of Epidemiology, German Institute for Human Nutrition, Potsdam, GermanyAnne Tjonneland - Danish Cancer Society Research Center, Copenhagen, DenmarkEmanuele Angelucci - Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, ItalySimonetta Di Lollo - Department of Surgery and Translational Medicine, Section of Anatomo-Pathology, University of Florence, Florence, ItalyMarco Rais - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, ItalyBrenda M Birmann - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USAFrancine Laden - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USAEdward Giovannucci - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USAPeter Kraft - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USAJinyan Huang - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USABaoshan Ma - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. College of Information Science and Technology, Dalian Maritime University, Dalian, ChinaYuanqing Ye - Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, USABrian C H Chiu - Department of Health Studies, University of Chicago, Chicago, Illinois, USAJoshua Sampson - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USALiming Liang - 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USAJu-Hyun Park - Dongguk University-Seoul, Seoul, South KoreaCharles C Chung - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USADennis D Weisenburger - Department of Pathology, City of Hope National Medical Center, Duarte, California, USANilanjan Chatterjee - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAJoseph F Fraumeni Jr - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USASusan L Slager - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USAXifeng Wu - Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, USASilvia de Sanjose - 1] Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainKarin E Smedby - Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenGilles Salles - 1] Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, CNRS, Pierre-Benite, France. Department of Hematology, Hospices Civils de Lyon, Pierre-Benite, France. Department of Hematology, Université Lyon 1, Pierre-Benite, FranceChristine F Skibola - 1] Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, Alabama, USA. Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USANathaniel Rothman - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAStephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.46(11), pp.1233-1238
- DOI
- 10.1038/ng.3105
- PMID
- 25261932
- PMCID
- PMC4213349
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 CA092153 / NCI NIH HHS R01 CA098661 / NCI NIH HHS UM1 CA167552 / NCI NIH HHS R01 CA154643 / NCI NIH HHS U01 HG007033 / NHGRI NIH HHS P30 CA033572 / NCI NIH HHS L30 CA162082 / NCI NIH HHS UL1 TR000135 / NCATS NIH HHS P01 CA087969 / NCI NIH HHS UL1 TR000430 / NCATS NIH HHS P42 ES004705 / NIEHS NIH HHS P30 CA008748 / NCI NIH HHS P30 CA086862 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS P30 CA015083 / NCI NIH HHS K07 CA115687 / NCI NIH HHS P50 CA097274 / NCI NIH HHS R01 CA098122 / NCI NIH HHS R25 CA098566 / NCI NIH HHS R01 CA149445 / NCI NIH HHS Intramural NIH HHS P30 CA016672 / NCI NIH HHS R01 CA129539 / NCI NIH HHS P30 CA016359 / NCI NIH HHS
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094373602771
Metrics
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