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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.

Authors :
Wang SS
Carrington M
Berndt SI
Slager SL
Bracci PM
Voutsinas J
Cerhan JR
Smedby KE
Hjalgrim H
Vijai J
Morton LM
Vermeulen R
Paltiel O
Vajdic CM
Linet MS
Nieters A
de Sanjose S
Cozen W
Brown EE
Turner J
Spinelli JJ
Zheng T
Birmann BM
Flowers CR
Becker N
Holly EA
Kane E
Weisenburger D
Maynadie M
Cocco P
Albanes D
Weinstein SJ
Teras LR
Diver WR
Lax SJ
Travis RC
Kaaks R
Riboli E
Benavente Y
Brennan P
McKay J
Delfau-Larue MH
Link BK
Magnani C
Ennas MG
Latte G
Feldman AL
Doo NW
Giles GG
Southey MC
Milne RL
Offit K
Musinsky J
Arslan AA
Purdue MP
Adami HO
Melbye M
Glimelius B
Conde L
Camp NJ
Glenn M
Curtin K
Clavel J
Monnereau A
Cox DG
Ghesquières H
Salles G
Bofetta P
Foretova L
Staines A
Davis S
Severson RK
Lan Q
Brooks-Wilson A
Smith MT
Roman E
Kricker A
Zhang Y
Kraft P
Chanock SJ
Rothman N
Hartge P
Skibola CF
Source :
Cancer research [Cancer Res] 2018 Jul 15; Vol. 78 (14), pp. 4086-4096. Date of Electronic Publication: 2018 May 07.
Publication Year :
2018

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. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR .<br /> (©2018 American Association for Cancer Research.)

Details

Language :
English
ISSN :
1538-7445
Volume :
78
Issue :
14
Database :
MEDLINE
Journal :
Cancer research
Publication Type :
Academic Journal
Accession number :
29735552
Full Text :
https://doi.org/10.1158/0008-5472.CAN-17-2900