HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

Abstract

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.

Metadata

Item Type:	Article
Authors/Creators:	Wang, Sophia S Carrington, Mary Berndt, Sonja I Slager, Susan L. Bracci, Paige M. Voutsinas, Jenna Cerhan, James R. Ekström Smedby, Karin Hjalgrim, Henrik Vijai, Joseph Morton, Lindsay M. Vermeulen, Roel Paltiel, Ora Vajdic, Claire M. Linet, Martha S. Nieters, Alexandra de Sanjosé, Silvia Cozen, Wendy Brown, Elizabeth E Turner, Jennifer Spinelli, John J. Zheng, Tongzhang Birmann, Brenda M Flowers, Christopher R Becker, Nikolaus Holly, Elizabeth A. Kane, Eleanor https://orcid.org/0000-0002-7438-9982 Weisenburger, Dennis Maynadie, Marc Cocco, Pierluigi Albanes, Demetrius Weinstein, Stephanie J Teras, Lauren R Diver, W Ryan Lax, Stephanie J https://orcid.org/0000-0002-7000-9364 Travis, Ruth C. Kaaks, Rudolf Riboli, Elio Benavente, Yolanda Brennan, Paul McKay, James D Delfau-Larue, Marie Helene Link, Brian K Magnani, Corrado Ennas, Maria Grazia Latte, Giancarlo Feldman, Andrew L Wong Doo, Nicole Giles, Graham G. Southey, Melissa C Milne, Roger L Offit, Kenneth Muskinsky, Jacob Arslan, Alan A Purdue, Mark P Adami, Hans Olov Melbye, Mads Glimelius, Bengt Conde, Lucia Camp, Nicola J Glenn, Martha Curtin, Karen Clavel, Jacqueline Monnereau, Alain Cox, David G Ghesquières, Hervé Salles, Gilles Boffetta, Paolo Foretova, Lenka Staines, Anthony Davis, Scott Severson, Richard K. Lan, Qing Brooks-Wilson, Angela Smith, Martyn T Roman, Eve https://orcid.org/0000-0001-7603-3704 Kricker, Anne Zhang, Yawei Kraft, Peter Chanock, Stephen J. Rothman, Nathaniel Hartge, Patricia Skibola, Christine F.
Copyright, Publisher and Additional Information:	©2018, American Association for Cancer Research. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy.
Keywords:	Journal Article
Dates:	Accepted: 24 April 2018 Published (online): 7 May 2018
Institution:	The University of York
Academic Units:	The University of York The University of York > Faculty of Sciences (York) > Health Sciences (York) The University of York > Faculty of Sciences (York) > Electronic Engineering (York)
Depositing User:	Pure (York)
Date Deposited:	24 May 2018 09:40
Last Modified:	15 Apr 2025 23:08
Published Version:	https://doi.org/10.1158/0008-5472.CAN-17-2900
Status:	Published online
Refereed:	Yes
Identification Number:	10.1158/0008-5472.CAN-17-2900
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:131260

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HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

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