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^*

^*Corresponding author for this work

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

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.

Original language	English
Pages (from-to)	45-59
Number of pages	15
Journal	International Journal of Cancer
Volume	158
Issue number	1
Early online date	5 Sept 2025
DOIs	https://doi.org/10.1002/ijc.70039
Publication status	Published - 1 Jan 2026

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Intl Journal of Cancer - 2025 - Moore - Genetically determined body mass index is associated with diffuse large B‐cellFinal published version, 1.85 MBLicence: CC BY

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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

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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 Hans-Olov Adami 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.",

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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, H-O, 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.

U2 - 10.1002/ijc.70039

DO - 10.1002/ijc.70039

M3 - Article

C2 - 40910475

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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