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

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

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
, Eleanor Kane
, Lauren R. Teras
, Mitchell J. Machiela
, Joshua Arias
, Orestis A. Panagiotou
, Alain Monnereau
, Nicole Wong Doo
, Zhaoming Wang
, Susan L. Slager
, Roel C.H. Vermeulen
, Claire M. Vajdic
, Karin E. Smedby
, John J. Spinelli
, Joseph Vijai
, Graham G. Giles
, Brian K. Link
, Alan A. Arslan
, Alexandra Nieters
, Paige M. Bracci

Nicola J. Camp, Gilles Salles, Wendy Cozen, Henrik Hjalgrim, Immaculata De Vivo, Hans Olov Adami, Demetrius Albanes, Nikolaus Becker, Yolanda Benavente, Simonetta Bisanzi, Paolo Boffetta, Paul Brennan, Angela R. Brooks-Wilson, Federico Canzian, Jacqueline Clavel, Lucia Conde, David G. Cox, Karen Curtin, Lenka Foretova, Hervé Ghesquières, Bengt Glimelius, Thomas M. Habermann, Jonathan N. Hofmann, Qing Lan, Mark Liebow, Anne Lincoln, Marc Maynadie, James McKay, Mads Melbye, Lucia Miligi, Roger L. Milne, Thierry J. Molina, Lindsay M. Morton, Kari E. North, Kenneth Offit, Marina Padoan, Sara Piro, Alpa V. Patel, Mark P. Purdue, Vignesh Ravichandran, Elio Riboli, Richard K. Severson, Melissa C. Southey, Anthony Staines, Lesley F. Tinker, Ruth C. Travis, Sophia S. Wang, Elisabete Weiderpass, Stephanie Weinstein, Tongzhang Zheng, Stephen J. Chanock, Nathaniel Rothman, Brenda M. Birmann, James R. Cerhan, Sonja I. Berndt

National Institutes of Health
University of York
American Cancer Society
United States Department of Health and Human Services
Brown University
Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
Centre Georges-François Leclerc
The University of Sydney
Cancer Council Victoria
St. Jude Children Research Hospital
Mayo Clinic Rochester, MN
Utrecht University
University of New South Wales
Karolinska Institutet
Provincial Health Services Authority
University of British Columbia
Memorial Sloan-Kettering Cancer Center
University of Melbourne
Monash University
University of Iowa
New York University
University of Freiburg
University of California at San Francisco
University of Utah
University of California at Irvine
Statens Serum Institut
University of Copenhagen
Danish Cancer Society
Brigham and Women’s Hospital
Harvard University
University of Oslo
German Cancer Research Center
Institute Catala Oncologia
CIBER Epidemiología y Salud Pública (CIBERESP)
Institute for the Study and Prevention of Cancer
International Agency for Research on Cancer
Simon Fraser University
CHU de Nancy
University College London
Centre Léon Bérard
Masaryk Memorial Cancer Institute
Hospices civils de Lyon
Universite Claude Bernard Lyon 1
Uppsala University
Université de Bourgogne
Norwegian University of Science and Technology
Stanford University
Centro Per Lo Studio E La Prevenzione Oncologica
Hopital Universitaire Robert Debre-APHP
University of North Carolina at Chapel Hill
University of Eastern Piedmont
Imperial College London
Wayne State University
Dublin City University
Fred Hutchinson Cancer Research Center
University of Oxford
City of Hope National Med Center

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English
Pages (from-to)	45-59
Number of pages	15
Journal	International Journal of Cancer
Volume	158
Issue number	1
DOIs	https://doi.org/10.1002/ijc.70039
State	Published - Jan 1 2026

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Moore, A., Kane, E., Teras, L. R., Machiela, M. J., Arias, J., Panagiotou, O. A., Monnereau, A., Doo, N. W., Wang, Z., Slager, S. L., Vermeulen, R. C. H., Vajdic, C. M., Smedby, K. E., Spinelli, J. J., Vijai, J., Giles, G. G., Link, B. K., Arslan, A. A., Nieters, A., ... Berndt, S. I. (2026). Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses. International Journal of Cancer, 158(1), 45-59. https://doi.org/10.1002/ijc.70039

@article{58eb4626445d4cc2afdd0339876f17ca,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 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.",

year = "2026",

month = jan,

day = "1",

doi = "10.1002/ijc.70039",

language = "English",

volume = "158",

pages = "45--59",

journal = "International Journal of Cancer",

issn = "0020-7136",

number = "1",

}

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, 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 2026, 'Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses', International Journal of Cancer, vol. 158, no. 1, pp. 45-59. https://doi.org/10.1002/ijc.70039

TY - JOUR

T1 - Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses

AU - Moore, Amy

AU - Kane, Eleanor

AU - Teras, Lauren R.

AU - Machiela, Mitchell J.

AU - Arias, Joshua

AU - Panagiotou, Orestis A.

AU - Monnereau, Alain

AU - Doo, Nicole Wong

AU - Wang, Zhaoming

AU - Slager, Susan L.

AU - Vermeulen, Roel C.H.

AU - Vajdic, Claire M.

AU - Smedby, Karin E.

AU - Spinelli, John J.

AU - Vijai, Joseph

AU - Giles, Graham G.

AU - Link, Brian K.

AU - Arslan, Alan A.

AU - Nieters, Alexandra

AU - Bracci, Paige M.

AU - Camp, Nicola J.

AU - Salles, Gilles

AU - Cozen, Wendy

AU - Hjalgrim, Henrik

AU - De Vivo, Immaculata

AU - Adami, Hans Olov

AU - Albanes, Demetrius

AU - Becker, Nikolaus

AU - Benavente, Yolanda

AU - Bisanzi, Simonetta

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Brooks-Wilson, Angela R.

AU - Canzian, Federico

AU - Clavel, Jacqueline

AU - Conde, Lucia

AU - Cox, David G.

AU - Curtin, Karen

AU - Foretova, Lenka

AU - Ghesquières, Hervé

AU - Glimelius, Bengt

AU - Habermann, Thomas M.

AU - Hofmann, Jonathan N.

AU - Lan, Qing

AU - Liebow, Mark

AU - Lincoln, Anne

AU - Maynadie, Marc

AU - McKay, James

AU - Melbye, Mads

AU - Miligi, Lucia

AU - Milne, Roger L.

AU - Molina, Thierry J.

AU - Morton, Lindsay M.

AU - North, Kari E.

AU - Offit, Kenneth

AU - Padoan, Marina

AU - Piro, Sara

AU - Patel, Alpa V.

AU - Purdue, Mark P.

AU - Ravichandran, Vignesh

AU - Riboli, Elio

AU - Severson, Richard K.

AU - Southey, Melissa C.

AU - Staines, Anthony

AU - Tinker, Lesley F.

AU - Travis, Ruth C.

AU - Wang, Sophia S.

AU - Weiderpass, Elisabete

AU - Weinstein, Stephanie

AU - Zheng, Tongzhang

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Birmann, Brenda M.

AU - Cerhan, James R.

AU - Berndt, Sonja I.

N1 - Publisher Copyright: © 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.

PY - 2026/1/1

Y1 - 2026/1/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105020930355

U2 - 10.1002/ijc.70039

DO - 10.1002/ijc.70039

M3 - Article

C2 - 40910475

AN - SCOPUS:105020930355

SN - 0020-7136

VL - 158

SP - 45

EP - 59

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 1

ER -

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

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