HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes.
Fiche publication
Date publication
mai 2018
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAYNADIE Marc
Tous les auteurs :
Wang SS, Carrington M, Berndt SI, Slager SL, Bracci PM, Voutsinas J, Cerhan JR, Ekström Smedby K, Hjalgrim H, Vijai J, Morton LM, Vermeulen R, Paltiel O, Vajdic CM, Linet MS, Nieters A, de Sanjosé 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 JD, Delfau-Larue MH, Link BK, Magnani C, Ennas MG, Latte G, Feldman AL, Wong Doo N, Giles GG, Southey MC, Milne RL, Offit K, Muskinsky 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, Boffetta 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
Lien Pubmed
Résumé
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.
Référence
Cancer Res.. 2018 May 7;: