OBJECTIVE: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. METHODS: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. RESULTS: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. CONCLUSIONS: These data suggest several plausible genetic links between DLBCL and SLE.

Arthritis and Clinical Immunology Research Program Oklahoma Medical Research Foundation Oklahoma City Oklahoma USA

BC Cancer Research Centre and School of Population and Public Health University of British Columbia Vancouver Canada

Cancer Epidemiology Centre Cancer Council Victoria Melbourne Australia

Cancer Epidemiology Research Programme Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Center for Chronic Immunodeficiency University Medical Center Freiburg Freiburg Germany

Centre for Big Data Research in Health University of New South Wales Sydney Australia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Melbourne Australia

Centre Heni Becquerel Université de Rouen Rouen France

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

Chronic Disease Prevention Unit National Institute for Health and Welfare Helsinki Finland

CIBER de Epidemiología y Salud Pública Barcelona Spain

Clinical Epidemiology Unit Department of Medicine Karolinska Institutet and Hematology Center Karolinska University Hospital Stockholm Sweden

Danish Cancer Society Research Center Copenhagen Denmark

Department of Biomedical Science University of Cagliari Monserrato Italy

Department of Biostatistics Yale School of Public Health New Haven USA

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

Department of Computational Biology St Jude Children's Research Hospital Memphis Tennessee USA

Department of Environmental and Occupational Health Dornsife School of Public Health at Drexel University Philadelphia USA

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

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

Department of Epidemiology Brown School of Public Health Providence USA

Department of Epidemiology German Institute for Human Nutrition Potsdam Germany

Department of Epidemiology Harvard T H Chan School of Public Health Boston USA

Department of Epidemiology School of Public Health and Comprehensive Cancer Center University of Alabama at Birmingham Birmingham USA

Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill USA

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

Department of Health Sciences Research Mayo Clinic Rochester USA

Department of Health Sciences University of York York UK

Department of Hematology Centre Léon Bérard Lyon France

Department of Hematology Hospices Civils de Lyon Pierre benite Cedex France

Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

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

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Medicine Mayo Clinic Rochester USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York USA

Department of Pathology AP HP Necker Enfants malades Université Paris Descartes Sorbonne Paris Cité France

Department of Population Health New York University School of Medicine New York USA

Department of Preventive Medicine USC Keck School of Medicine University of Southern California Los Angeles USA

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

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

Division of Biomedical Statistics and Informatics Department of Health Sciences Research Mayo Clinic Jacksonville USA

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda USA

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Cancer Etiology Department of Population Sciences Beckman Research Institute Duarte USA

Division of Clinical Epidemiology Research Institute of the McGill University Health Centre Montreal Canada

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

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

Division of Hematology Department of Medicine Mayo Clinic Rochester USA

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

Division of Rheumatology Immunology and Allergy Brigham and Women's Hospital Boston USA

Division of Rheumatology University of Calgary Calgary Canada

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

Epidemiology of childhood and adolescent cancers Group Inserm Center of Research in Epidemiology and Statistics Sorbonne Paris Cité Paris France

Epidemiology Research Program American Cancer Society Atlanta USA

Faculty of Medicine and Health Sciences Macquarie University Sydney Australia

Feinberg School of Medicine Northwestern University Chicago USA

Genetic Epidemiology Laboratory Department of Pathology University of Melbourne Melbourne Australia

Genome Sciences Centre BC Cancer Agency Vancouver Canada

Hematology Unit Ospedale Oncologico di Riferimento Regionale 'A Businco' Cagliari Italy

Human Genetics Foundation Turin Italy

Icahn Institute for Genomics and Multiscale Biology Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York USA

INSERM U1052 Cancer Research Center of Lyon Centre Léon Bérard Lyon France

Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands

International Agency for Research on Cancer Lyon France

Lymphoid Malignancies Unit Henri Mondor Hospital and University Paris Est Créteil France

MRC PHE Centre for Environment and Health School of Public Health Imperial College London London UK

Ontario Health Study Toronto Canada

Registre des Hémopathies Malignes de Côte d'Or EA 4184 Univ Bourgogne Franche Comté and Dijon University Hospital Dijon France

School of Nursing and Human Sciences Dublin City University Dublin Ireland

Slone Epidemiology Center Boston University Boston USA

Sydney School of Public Health The University of Sydney Sydney Australia

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

Westat Inc Rockville USA

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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes