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Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Authors

Moore A, Kane E, Teras LR, Machiela MJ, Arias J, Panagiotou OA, Monnereau A, Doo NW, Wang Z, Slager SL, Vermeulen RCH, Vajdic CM, Smedby KE, Spinelli JJ, Vijai J, Giles GG, Link BK, Arslan AA, Nieters A, Bracci PM, ...show more Camp NJ, Salles G, Cozen W, Hjalgrim H, De Vivo I, Adami HO, Albanes D, Becker N, Benavente Y, Bisanzi S, Boffetta P, Brennan P, Brooks-Wilson AR, Canzian F, Clavel J, Conde L, Cox DG, Curtin K, Foretova L, Ghesquières H, Glimelius B, Habermann TM, Hofmann JN, Lan Q, Liebow M, Lincoln A, Maynadie M, McKay J, Melbye M, Miligi L, Milne RL, Molina TJ, Morton LM, North KE, Offit K, Padoan M, Piro S, Patel AV, Purdue MP, Ravichandran V, Riboli E, Severson RK, Southey MC, Staines A, Tinker LF, Travis RC, Wang SS, Weiderpass E, Weinstein S, Zheng T, Chanock SJ, Rothman N, Birmann BM, Cerhan JR, Berndt SI

Affiliations

  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Department of Health Sciences, University of York, York, UK.
  • Department of Population Science, American Cancer Society, Atlanta, Georgia, USA.
  • Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA.
  • Unit of Mixed Research (UMR1153), Centre for Research in Epidemiology and Statistics (CRESS), INSERM, Université Paris-Cité, Paris, France.
  • Concord Clinical School, University of Sydney, Concord, New South Wales, Australia.
  • Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
  • Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
  • Surveillance and Evaluation Research Program, The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
...show more
  • Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
  • Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
  • Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.
  • Center for Chronic Immunodeficiency, Institute for Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany.
  • Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
  • Department of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
  • School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
  • Division of Hematology-Oncology, Department of Medicine, University of California Irvine, Orange, California, USA.
  • Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
  • Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
  • Regional Laboratory for Cancer Prevention, Institute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, Italy.
  • Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.
  • Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC), Lyon, France.
  • Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
  • Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, Lyon, France.
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
  • 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, Mayo Clinic, Rochester, Minnesota, USA.
  • INSERM U1231, EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France.
  • Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
  • Department of Pathology, APHP, Necker and Robert Debré, Université Paris Cité, Institut Imagine, INSERM U1163, Paris, France.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Unit of Medical Statistics and Epidemiology, Department Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro", Novara, Italy.
  • Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, UK.
  • Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA.
  • School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, DC, USA.
  • Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
  • Division of Health Analytics, City of Hope Beckman Research Institute, Duarte, California, USA.
  • Department of Epidemiology, Brown University, Providence, Rhode Island, USA.
  • Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Abstract

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.

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Publication Details

PubMed ID
40910475

Digital Object Identifier
10.1002/ijc.70039

Publication
Int J Cancer. 2026 Jan 1; Volume 158 (Issue 1): Pages 45-59

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