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


Authors: Wang, S. S.; Carrington, M.; Berndt, S. I.; Slager, S. L.; Bracci, P. M.; Voutsinas, J.; Cerhan, J. R.; Smedby, K. E.; Hjalgrim, H.; Vijai, J.; Morton, L. M.; Vermeulen, R.; Paltiel, O.; Vajdic, C. M.; Linet, M. S.; Nieters, A.; de Sanjose, S.; Cozen, W.; Brown, E. E.; Turner, J.; Spinelli, J. J.; Zheng, T.; Birmann, B. M.; Flowers, C. R.; Becker, N.; Holly, E. A.; Kane, E.; Weisenburger, D.; Maynadie, M.; Cocco, P.; Albanes, D.; Weinstein, S. J.; Teras, L. R.; Diver, W. R.; Lax, S. J.; Travis, R. C.; Kaaks, R.; Riboli, E.; Benavente, Y.; Brennan, P.; McKay, J.; Delfau-Larue, M. H.; Link, B. K.; Magnani, C.; Ennas, M. G.; Latte, G.; Feldman, A. L.; Doo, N. W.; Giles, G. G.; Southey, M. C.; Milne, R. L.; Offit, K.; Musinsky, J.; Arslan, A. A.; Purdue, M. P.; Adami, H. O.; Melbye, M.; Glimelius, B.; Conde, L.; Camp, N. J.; Glenn, M.; Curtin, K.; Clavel, J.; Monnereau, A.; Cox, D. G.; Ghesquières, H.; Salles, G.; Bofetta, P.; Foretova, L.; Staines, A.; Davis, S.; Severson, R. K.; Lan, Q.; Brooks-Wilson, A.; Smith, M. T.; Roman, E.; Kricker, A.; Zhang, Y.; Kraft, P.; Chanock, S. J.; Rothman, N.; Hartge, P.; Skibola, C. F.
Article Title: 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. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. © 2018 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 78
Issue: 14
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2018-07-15
Start Page: 4086
End Page: 4096
Language: English
DOI: 10.1158/0008-5472.can-17-2900
PROVIDER: scopus
PMCID: PMC6065509
PUBMED: 29735552
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    485 Offit
  2. Vijai Joseph
    112 Joseph