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.

] Cancer Control Research BC Cancer Agency Vancouver British Columbia Canada [2] School of Population and Public Health University of British Columbia Vancouver British Columbia Canada

] Cancer Epidemiology Centre Cancer Council Victoria Melbourne Victoria Australia [2] Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton Victoria Australia

] Department of Environmental and Occupational Health Drexel University School of Public Health Philadelphia Pennsylvania USA [2] Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Bureau of Epidemiologic Research Academy of Athens Athens Greece [3] Hellenic Health Foundation Athens Greece

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA [3] Department of Environmental Health Harvard School of Public Health Boston Massachusetts USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA [3] Department of Nutrition Harvard School of Public Health Boston Massachusetts USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] College of Information Science and Technology Dalian Maritime University Dalian China

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Department of Biostatistics Harvard School of Public Health Boston Massachusetts USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA [2] Medical Research Council Centre for Environment and Health School of Public Health Imperial College London London UK

] Department of Epidemiology Research Division of Health Surveillance and Research Statens Serum Institut Copenhagen Denmark [2] Department of Medicine Stanford University School of Medicine Stanford California USA

] Department of Epidemiology School of Public Health and Comprehensive Cancer Center Birmingham Alabama USA [2] Division of Environmental Health Sciences University of California Berkeley School of Public Health Berkeley California USA

] Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill North Carolina USA [2] Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

] Department of Hematology Centre Léon Bérard Lyon France [2] Laboratoire de Biologie Moléculaire de la Cellule UMR 5239 CNRS Pierre Benite France

] Department of Medical Genetics and of Epidemiology University Medical Center Utrecht Utrecht the Netherlands [2] Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht the Netherlands

] Department of Oncology and Pathology Karolinska Institutet Karolinska University Hospital Solna Stockholm Sweden [2] Department of Radiology Oncology and Radiation Science Uppsala University Uppsala Sweden

] Department of Population Health New York University School of Medicine New York New York USA [2] Cancer Institute New York University School of Medicine New York New York USA

] Department of Preventive Medicine University of Southern California Keck School of Medicine University of Southern California Los Angeles California USA [2] Norris Comprehensive Cancer Center University of Southern California Keck School of Medicine University of Southern California Los Angeles California USA

] Environmental Epidemiology of Cancer Group INSERM Centre for Research in Epidemiology and Population Health Villejuif France [2] UMRS 1018 Université Paris Sud Villejuif France

] Environmental Epidemiology of Cancer Group INSERM Centre for Research in Epidemiology and Population Health Villejuif France [2] UMRS 1018 Université Paris Sud Villejuif France [3] Registre des Hémopathies Malignes de la Gironde Institut Bergonié Bordeaux France

] Genome Sciences Centre BC Cancer Agency Vancouver British Columbia Canada [2] Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby British Columbia Canada

] Human Genetics Foundation Turin Italy [2] Cancer Epidemiology Centre Cancer Council Victoria Melbourne Victoria Australia [3] Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton Victoria Australia

] Human Genetics Foundation Turin Italy [2] Medical Research Council Centre for Environment and Health School of Public Health Imperial College London London UK

] Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht the Netherlands [2] Institute for Risk Assessment Sciences Utrecht University Utrecht the Netherlands

] Laboratoire de Biologie Moléculaire de la Cellule UMR 5239 CNRS Pierre Benite France [2] Department of Hematology Hospices Civils de Lyon Pierre Benite France [3] Department of Hematology Université Lyon 1 Pierre Benite France

] Pathology Australian School of Advanced Medicine Macquarie University Sydney New South Wales Australia [2] Department of Histopathology Douglass Hanly Moir Pathology Macquarie Park New South Wales Australia

] Unit of Infections and Cancer Barcelona Spain

Cancer Genomics Research Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute Gaithersburg Maryland USA

Center for Chronic Immunodeficiency University Medical Center Freiburg Freiburg Germany

Centre Heni Becquerel Rouen France

Centre National de Génotypage Evry France

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA

Danish Cancer Society Research Center Copenhagen Denmark

Department of Biomedical Science University of Cagliari Monserrato Italy

Department of Biostatistics University of Alabama at Birmingham Birmingham Alabama USA

Department of Biostatistics Yale School of Public Health New Haven Connecticut USA

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and Masaryk University Brno Czech Republic

Department of Cancer Etiology City of Hope Beckman Research Institute Duarte California USA

Department of Chronic Disease Prevention National Institute for Health and Welfare Helsinki Finland

Department of Environmental Health Sciences Yale School of Public Health New Haven Connecticut USA

Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California USA

Department of Epidemiology German Institute for Human Nutrition Potsdam Germany

Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA

Department of Epidemiology MD Anderson Cancer Center Houston Texas USA

Department of Epidemiology Research Division of Health Surveillance and Research Statens Serum Institut Copenhagen Denmark

Department of Family Medicine and Public Health Sciences Wayne State University Detroit Michigan USA

Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA

Department of Health Sciences University of York York UK

Department of Health Studies University of Chicago Chicago Illinois USA

Department of Hematology Centre Hospitalier Universitaire Henri Mondor Creteil France

Department of Internal Medicine Carver College of Medicine The University of Iowa Iowa City Iowa USA

Department of Laboratory Medicine and Pathology Memorial Sloan Kettering Cancer Center New York New York USA

Department of Medicine Mayo Clinic Rochester Minnesota USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA

Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Department of Pathology City of Hope National Medical Center Duarte California USA

Department of Pathology Necker Enfants Malades Université Paris Descartes Sorbonne Paris Cité Paris France

Department of Pathology University of Melbourne Parkville Victoria Australia

Department of Public Health Clinical and Molecular Medicine University of Cagliari Monserrato Italy

Department of Surgery and Translational Medicine Section of Anatomo Pathology University of Florence Florence Italy

Division of Biomedical Statistics and Informatics Mayo Clinic Jacksonville Florida USA

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland USA

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Endocrinology Diabetes and Metabolism Ohio State University Columbus Ohio USA

Division of Environmental Health Sciences University of California Berkeley School of Public Health Berkeley California USA

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington USA

Dongguk University Seoul Seoul South Korea

Epidemiology Research Program American Cancer Society Atlanta Georgia USA

Genetic Cancer Susceptibility Group Section of Genetics International Agency for Research on Cancer Lyon France

Group of Genetic Epidemiology Section of Genetics International Agency for Research on Cancer Lyon France

Health Studies Sector Westat Rockville Maryland USA

Hematology Unit Ospedale Oncologico di Riferimento Regionale A Businco Cagliari Italy

Lyon France

Prince of Wales Clinical School University of New South Wales Sydney New South Wales Australia

Registre des Hémopathies Malignes de Côte d'Or University of Burgundy and Dijon University Hospital Dijon France

School of Nursing and Human Sciences Dublin City University Dublin Ireland

School of Public Health Imperial College London London UK

Sydney School of Public Health University of Sydney Sydney New South Wales Australia

Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York USA

Winship Cancer Institute Emory University School of Medicine Atlanta Georgia USA

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The EHA Research Roadmap: Malignant Lymphoid Diseases

B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

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A genome-wide association study of marginal zone lymphoma shows association to the HLA region