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

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<sub>per SD</sub> = 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

Journal
International Journal of Cancer
Published
2025-09-05
DOI
https://doi.org/10.1002/ijc.70039
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Lindsay McOmber Morton, Mads Melbye, Angela Brooks‐Wilson, Federico Canzian et al.
International Journal of Cancer
Genetic Associations and Epidemiology
article

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

Lindsay McOmber Morton, Mads Melbye, Angela Brooks‐Wilson, Federico Canzian, Anne Lincoln, Eleanor Kane, Joseph Vijai, Marina Padoan, Alpa V. Patel, David G. Cox, Graham G. Giles, Mark P. Purdue, Karin E. Smedby, Paolo Boffetta, Brenda M. Birmann, Lucia Miligi, Sophia Wang, Alan A. Arslan, Thomas Matthew Habermann, Hans‐Olov Adami, Lauren R. Teras, Marc Maynadié, Roel C.H. Vermeulen, Ruth C. Travis, Claire M. Vajdic, Lucía Conde, Amy Moore, Nathaniel Rothman, Stephanie J. Weinstein, Roger Laughlin Milne, Lenka Foretová, Alexandra Nieters, Wendy Cozen, Immaculata De Vivo, Anthony Staines, Jonathan N. Hofmann, Alain Monnereau, Lesley F. Tinker, Simonetta Bisanzi, Kari E. North, Sonja I. Berndt, Susan L. Slager, Elio Ríboli, Joshua Arias, Nicola J. Camp, Mitchell J. Machiela, James R. Cerhan, Vignesh Ravichandran, Paul E. Brennan, Jacqueline Clavel, Nicole Wong Doo, Orestis A. Panagiotou, Mark Liebow, Elisabete Weiderpass, Brian K. Link, Thierry Jo Molina, Karen Curtin, Gilles Salles, Henrik Hjalgrim, James McKay, Melissa C. Southey, Sara Piro, Qing Lan, Zhaoming Wang, Yolanda Benavente, Hervé Ghesquières, Stephen J. Chanock, John J. Spinelli, Kenneth Offit, Paige M. Bracci, Tongzhang Zheng, Nikolaus Becker, Richard K. Severson, Demetrius Albanes, Bengt Glimelius
article en

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<sub>per SD</sub> = 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.

International Journal of CancerVol. 158(1)
Université Claude Bernard Lyon 1 (FR), Statens Serum Institut (DK), École Normale Supérieure de Lyon (FR), University of North Carolina at Chapel Hill (US), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Uppsala University (SE), University of Copenhagen (DK), University of Iowa (US), Brigham and Women's Hospital (US), American Cancer Society (US), Centre National de la Recherche Scientifique (FR), The University of Sydney (AU), City Of Hope National Medical Center (US), St. Jude Children's Research Hospital (US), Mayo Clinic (US), NSW Ambulance (AU), Memorial Sloan Kettering Cancer Center (US), Karolinska University Hospital (SE), Harvard University (US), University of British Columbia (CA), Inserm (FR), The University of Melbourne (AU), Université de Bourgogne (FR), German Cancer Research Center (DE), Simon Fraser University (CA), University of California, San Francisco (US), University of Oslo (NO), Wayne State University (US), Utrecht University (NL), Cancer Council Victoria (AU), University of California, Irvine (US), Université Paris Cité (FR), Norwegian University of Science and Technology (NO), Heidelberg University (DE), Brown University (US), Concord Repatriation General Hospital (AU), Huntsman Cancer Institute (US), University Medical Center Freiburg (DE), Cancer Research UK (GB), Prevention Institute (US), Rigshospitalet (DK), Karolinska Institutet (SE), University Medical Center Utrecht (NL), University of Oxford (GB), NYU Langone Health (US), Fred Hutch Cancer Center (US), Sorbonne Paris Cité (FR), University of California, Irvine Medical Center (US), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Institut Català d'Oncologia (ES), City of Hope (US), Hôpital Lyon Sud (FR), Masaryk Memorial Cancer Institute (CZ), Monash Health (AU), Centre de Recherche en Cancérologie de Lyon (FR), Genome British Columbia (CA), Canada's Michael Smith Genome Sciences Centre (CA), Institut Bergonié (FR), National Cancer Institute (US), Maison des Sciences sociales et des Humanités de Dijon (FR), Mayo Clinic in Florida (US), CRUK Lung Cancer Centre of Excellence (GB), Danish Cancer Society (DK), Piedmont Reference Center for Epidemiology and Cancer Prevention (IT), Canadian Centre for Applied Research in Cancer Control (CA), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Cancer Research UK Oxford Centre (GB), Melbourne Health (AU), Centre International de Recherche en Infectiologie (FR), Hôpital Paul-Brousse (FR), Institut des Maladies Génétiques Imagine (FR), Centre international de recherche sur le cancer (FR), Dublin City University (IE), Centre de Recherche Épidémiologie et Statistique (FR), Division of Cancer Epidemiology and Genetics, University College London (GB), Imperial College London (GB), University of York (GB), Monash University (AU), New York University (US), Stony Brook University (US), University of Bologna (IT), Stanford University (US)
U.S. Department of Health and Human Services, World Health Organization, Centre International de Recherche sur le Cancer, Michael Smith Health Research BC, National Institutes of Health, Centers for Disease Control and Prevention, Canadian Institutes of Health Research, National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Cancer Institute
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Genetic Associations and Epidemiology
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