Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (ORper SD = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

Bill Lyons Informatics Centre UCL Cancer Institute University College London London UK

Cancer Control Research BC Cancer Vancouver British Columbia Canada

Cancer Epidemiology and Prevention Research Unit School of Public Health Imperial College London London UK

Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

Cancer Epidemiology Research Programme Catalan Institute of Oncology IDIBELL Barcelona Spain

Cancer Epidemiology Unit University of Oxford Oxford UK

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

Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

Center for Chronic Immunodeficiency Institute for Immunodeficiency University Medical Center Freiburg Freiburg Baden Württemberg Germany

Center for Gerontology and Healthcare Research Brown University School of Public Health Providence Rhode Island USA

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

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

CIRI Centre International de Recherche en Infectiologie Team Lymphoma Immuno Biology Univ Lyon Inserm U1111 Université Claude Bernard Lyon 1 CNRS UMR5308 ENS de Lyon Lyon France

Concord Clinical School University of Sydney Concord New South Wales Australia

Danish Cancer Institute Danish Cancer Society Copenhagen Denmark

Danish Cancer Society Research Center Danish Cancer Society Copenhagen Denmark

Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby British Columbia Canada

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

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Pathology Melbourne Medical School The University of Melbourne Melbourne Victoria Australia

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

Department of Environmental Medicine New York University School of Medicine New York New York USA

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

Department of Epidemiology Brown University Providence Rhode Island USA

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

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

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

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

Department of Genetics Stanford University Medical School Stanford California USA

Department of Haematology Rigshospitalet Copenhagen Denmark

Department of Health Sciences University of York York UK

Department of Health Services Policy and Practice Brown University School of Public Health Providence Rhode Island USA

Department of Hematology Hospices Civils de Lyon Lyon Sud Hospital Pierre Benite France

Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Internal Medicine and Huntsman Cancer Institute University of Utah School of Medicine Salt Lake City Utah USA

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

Department of Internal Medicine Mayo Clinic Rochester Minnesota USA

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

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

Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Department of Obstetrics and Gynecology New York University School of Medicine New York New York USA

Department of Pathology APHP Necker and Robert Debré Université Paris Cité Institut Imagine INSERM U1163 Paris France

Department of Population Health Sciences Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands

Department of Population Science American Cancer Society Atlanta Georgia USA

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

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Baden Württemberg Germany

Division of Health Analytics City of Hope Beckman Research Institute Duarte California USA

Division of Hematology Oncology Department of Medicine University of California Irvine Orange California USA

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

Environmental and Occupational Epidemiology Unit Cancer Prevention and Research Institute Florence Italy

Genome Sciences Centre BC Cancer Vancouver British Columbia Canada

Genomic Epidemiology Branch International Agency for Research on Cancer Lyon France

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Hematology Center Karolinska University Hospital Stockholm Sweden

INSERM U1231 EA 4184 Registre des Hémopathies Malignes de Côte d'Or University of Burgundy and Dijon University Hospital Dijon France

Institute of Health and Society Clinical Effectiveness Research Group University of Oslo Oslo Norway

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands

Laboratory of Translational Genomics Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland USA

Medicine and Health Sciences Department Jebsen Center for Genetic Epidemiology NTNU Trondheim Norway

National Registry of Childhood Cancers APHP CHU Paul Brousse Villejuif and CHU de Nancy France

Perlmutter Cancer Center NYU Langone Medical Center New York New York USA

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Victoria Australia

Quantitative Health Sciences Mayo Clinic Rochester Minnesota USA

Regional Laboratory for Cancer Prevention Institute for Cancer Research Prevention and Oncological Network Florence Italy

Registre des hémopathies malignes de la Gironde Institut Bergonié Bordeaux Cedex France

School of Nursing Psychotherapy and Community Health Dublin City University Dublin Ireland

School of Population and Public Health University of British Columbia Vancouver British Columbia Canada

Stony Brook Cancer Center Stony Brook University Stony Brook New York USA

Surveillance and Evaluation Research Program The Kirby Institute University of New South Wales Sydney New South Wales Australia

Unidad de Infecciones y Cáncer CIBER de Epidemiología y Salud Pública Barcelona Spain

Unit of Medical Statistics and Epidemiology Department Translational Medicine University of Eastern Piedmont Amedeo Avogadro Novara Italy

Unit of Mixed Research INSERM Université Paris Cité Paris France

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