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

Amy Moore¹, Eleanor Kane², Lauren R Teras³, Mitchell J Machiela¹, Joshua Arias¹, Orestis A Panagiotou^{4

5}, Alain Monnereau^{6

7}, Nicole Wong Doo^{8

9}, Zhaoming Wang^{10

11}, Susan L Slager¹², Roel C H Vermeulen^{13

14}, Claire M Vajdic¹⁵, Karin E Smedby^{16

17}, John J Spinelli^{18

19}, Joseph Vijai²⁰, Graham G Giles^{9

21

22}, Brian K Link²³, Alan A Arslan^{24

25

26}, Alexandra Nieters²⁷, Paige M Bracci²⁸, Nicola J Camp²⁹, Gilles Salles¹⁹, Wendy Cozen³⁰, Henrik Hjalgrim^{31

32

33

34}, Immaculata De Vivo^{35

36}, Hans-Olov Adami^{36

37

38}, Demetrius Albanes¹, Nikolaus Becker³⁹, Yolanda Benavente^{40

41}, Simonetta Bisanzi⁴², Paolo Boffetta^{43

44}, Paul Brennan⁴⁵, Angela R Brooks-Wilson^{46

47}, Federico Canzian⁴⁸, Jacqueline Clavel^{6

49}, Lucia Conde⁵⁰, David G Cox⁵¹, Karen Curtin²⁹, Lenka Foretova⁵², Hervé Ghesquières^{53

54}, Bengt Glimelius⁵⁵, Thomas M Habermann⁵⁶, Jonathan N Hofmann¹, Qing Lan¹, Mark Liebow⁵⁶, Anne Lincoln¹⁹, Marc Maynadie⁵⁷, James McKay⁴⁵, Mads Melbye^{32

58

59

60}, Lucia Miligi⁶¹, Roger L Milne^{9

21

22}, Thierry J Molina⁶², Lindsay M Morton¹, Kari E North^{63

64}, Kenneth Offit¹⁹, Marina Padoan⁶⁵, Sara Piro⁶¹, Alpa V Patel¹⁹, Mark P Purdue¹, Vignesh Ravichandran¹⁹, Elio Riboli⁶⁶, Richard K Severson⁶⁷, Melissa C Southey^{9

22

68}, Anthony Staines⁶⁹, Lesley F Tinker⁷⁰, Ruth C Travis⁷¹, Sophia S Wang⁷², Elisabete Weiderpass⁴⁵, Stephanie Weinstein¹, Tongzhang Zheng⁷³, Stephen J Chanock¹, Nathaniel Rothman¹, Brenda M Birmann³⁵, James R Cerhan¹¹, Sonja I Berndt¹

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
² Department of Health Sciences, University of York, York, UK.
³ Department of Population Science, American Cancer Society, Atlanta, Georgia, USA.
⁴ Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA.
⁵ Center for Gerontology and Healthcare Research, Brown University School of Public Health, Providence, Rhode Island, USA.
⁶ Unit of Mixed Research (UMR1153), Centre for Research in Epidemiology and Statistics (CRESS), INSERM, Université Paris-Cité, Paris, France.
⁷ Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex, France.
⁸ Concord Clinical School, University of Sydney, Concord, New South Wales, Australia.
⁹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰ Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹² Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
¹⁴ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁵ Surveillance and Evaluation Research Program, The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
¹⁸ Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.
¹⁹ School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²¹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
²² Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²³ Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
²⁴ Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.
²⁵ Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.
²⁶ Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York, USA.
²⁷ Center for Chronic Immunodeficiency, Institute for Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany.
²⁸ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
²⁹ Department of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
³⁰ Division of Hematology-Oncology, Department of Medicine, University of California Irvine, Orange, California, USA.
³¹ Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
³² Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
³³ Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
³⁴ Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
³⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³⁶ Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA.
³⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁸ Institute of Health and Society, Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway.
³⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
⁴⁰ Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
⁴¹ Unidad de Infecciones y Cáncer, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁴² Regional Laboratory for Cancer Prevention, Institute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, Italy.
⁴³ Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.
⁴⁴ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁴⁵ Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC), Lyon, France.
⁴⁶ Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
⁴⁷ Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
⁴⁸ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁹ National Registry of Childhood Cancers, APHP, CHU Paul Brousse, Villejuif and CHU de Nancy, France.
⁵⁰ Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
⁵¹ Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, Lyon, France.
⁵² Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵³ Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre Benite, France.
⁵⁴ 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.
⁵⁵ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁵⁶ Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁵⁷ INSERM U1231, EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France.
⁵⁸ Medicine and Health Sciences Department, Jebsen Center for Genetic Epidemiology, NTNU, Trondheim, Norway.
⁵⁹ Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark.
⁶⁰ Department of Genetics, Stanford University Medical School, Stanford, California, USA.
⁶¹ Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
⁶² Department of Pathology, APHP, Necker and Robert Debré, Université Paris Cité, Institut Imagine, INSERM U1163, Paris, France.
⁶³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶⁴ Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶⁵ Unit of Medical Statistics and Epidemiology, Department Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro", Novara, Italy.
⁶⁶ Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, UK.
⁶⁷ Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA.
⁶⁸ Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
⁶⁹ School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland.
⁷⁰ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, DC, USA.
⁷¹ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
⁷² Division of Health Analytics, City of Hope Beckman Research Institute, Duarte, California, USA.
⁷³ Department of Epidemiology, Brown University, Providence, Rhode Island, USA.

PMID: 40910475
DOI: 10.1002/ijc.70039

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

Amy Moore et al. Int J Cancer. 2025.

. 2025 Sep 5.

doi: 10.1002/ijc.70039. Online ahead of print.

Authors

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
² Department of Health Sciences, University of York, York, UK.
³ Department of Population Science, American Cancer Society, Atlanta, Georgia, USA.
⁴ Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA.
⁵ Center for Gerontology and Healthcare Research, Brown University School of Public Health, Providence, Rhode Island, USA.
⁶ Unit of Mixed Research (UMR1153), Centre for Research in Epidemiology and Statistics (CRESS), INSERM, Université Paris-Cité, Paris, France.
⁷ Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex, France.
⁸ Concord Clinical School, University of Sydney, Concord, New South Wales, Australia.
⁹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰ Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹² Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
¹⁴ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁵ Surveillance and Evaluation Research Program, The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
¹⁸ Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.
¹⁹ School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²¹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
²² Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²³ Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
²⁴ Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.
²⁵ Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.
²⁶ Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York, USA.
²⁷ Center for Chronic Immunodeficiency, Institute for Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany.
²⁸ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
²⁹ Department of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
³⁰ Division of Hematology-Oncology, Department of Medicine, University of California Irvine, Orange, California, USA.
³¹ Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
³² Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
³³ Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
³⁴ Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
³⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³⁶ Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USA.
³⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³⁸ Institute of Health and Society, Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway.
³⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
⁴⁰ Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
⁴¹ Unidad de Infecciones y Cáncer, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
⁴² Regional Laboratory for Cancer Prevention, Institute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, Italy.
⁴³ Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.
⁴⁴ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁴⁵ Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC), Lyon, France.
⁴⁶ Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
⁴⁷ Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
⁴⁸ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴⁹ National Registry of Childhood Cancers, APHP, CHU Paul Brousse, Villejuif and CHU de Nancy, France.
⁵⁰ Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, UK.
⁵¹ Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, Lyon, France.
⁵² Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
⁵³ Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre Benite, France.
⁵⁴ 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.
⁵⁵ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁵⁶ Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁵⁷ INSERM U1231, EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France.
⁵⁸ Medicine and Health Sciences Department, Jebsen Center for Genetic Epidemiology, NTNU, Trondheim, Norway.
⁵⁹ Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark.
⁶⁰ Department of Genetics, Stanford University Medical School, Stanford, California, USA.
⁶¹ Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
⁶² Department of Pathology, APHP, Necker and Robert Debré, Université Paris Cité, Institut Imagine, INSERM U1163, Paris, France.
⁶³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶⁴ Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶⁵ Unit of Medical Statistics and Epidemiology, Department Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro", Novara, Italy.
⁶⁶ Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, UK.
⁶⁷ Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA.
⁶⁸ Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
⁶⁹ School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland.
⁷⁰ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, DC, USA.
⁷¹ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
⁷² Division of Health Analytics, City of Hope Beckman Research Institute, Duarte, California, USA.
⁷³ Department of Epidemiology, Brown University, Providence, Rhode Island, USA.

PMID: 40910475
DOI: 10.1002/ijc.70039

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 (OR_{per 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.

© 2025 International Agency for Research on Cancer; licensed by UICC and The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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

Affiliations

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

Authors

Affiliations

Abstract

References

REFERENCES

Grants and funding

LinkOut - more resources

Full Text Sources