By the same authors

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

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  • Sophia S Wang
  • Mary Carrington
  • Sonja I Berndt
  • Susan L. Slager
  • Paige M. Bracci
  • Jenna Voutsinas
  • James R. Cerhan
  • Karin Ekström Smedby
  • Henrik Hjalgrim
  • Joseph Vijai
  • Lindsay M. Morton
  • Roel Vermeulen
  • Ora Paltiel
  • Claire M. Vajdic
  • Martha S. Linet
  • Alexandra Nieters
  • Silvia de Sanjosé
  • Wendy Cozen
  • Elizabeth E Brown
  • Jennifer Turner
  • John J. Spinelli
  • Tongzhang Zheng
  • Brenda M Birmann
  • Christopher R Flowers
  • Nikolaus Becker
  • Elizabeth A. Holly
  • Dennis Weisenburger
  • Marc Maynadie
  • Pierluigi Cocco
  • Demetrius Albanes
  • Stephanie J Weinstein
  • Lauren R Teras
  • W Ryan Diver
  • Ruth C. Travis
  • Rudolf Kaaks
  • Elio Riboli
  • Yolanda Benavente
  • Paul Brennan
  • James D McKay
  • Marie Helene Delfau-Larue
  • Brian K Link
  • Corrado Magnani
  • Maria Grazia Ennas
  • Giancarlo Latte
  • Andrew L Feldman
  • Nicole Wong Doo
  • Graham G. Giles
  • Melissa C Southey
  • Roger L Milne
  • Kenneth Offit
  • Jacob Muskinsky
  • Alan A Arslan
  • Mark P Purdue
  • Hans Olov Adami
  • Mads Melbye
  • Bengt Glimelius
  • Lucia Conde
  • Nicola J Camp
  • Martha Glenn
  • Karen Curtin
  • Jacqueline Clavel
  • Alain Monnereau
  • David G Cox
  • Hervé Ghesquières
  • Gilles Salles
  • Paolo Boffetta
  • Lenka Foretova
  • Anthony Staines
  • Scott Davis
  • Richard K. Severson
  • Qing Lan
  • Angela Brooks-Wilson
  • Martyn T Smith
  • Anne Kricker
  • Yawei Zhang
  • Peter Kraft
  • Stephen J. Chanock
  • Nathaniel Rothman
  • Patricia Hartge
  • Christine F. Skibola


Publication details

JournalCancer research
DateAccepted/In press - 24 Apr 2018
DateE-pub ahead of print (current) - 7 May 2018
Number of pages32
Early online date7/05/18
Original languageEnglish


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.

Bibliographical note

©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.

    Research areas

  • Journal Article

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