Wang, Sophia S, Carrington, Mary, Berndt, Sonja I et al. (80 more authors) (2018) HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes. Cancer research. ISSN 1538-7445
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 |
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Authors/Creators: |
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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: |
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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: | 16 Oct 2024 14:45 |
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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Description: HLA class I & II diversity contributes to the etiologic hetrogenicity of non-hodgekin lymphoma subtypes