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RESEARCH PRODUCT

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

Roel VermeulenPaulo BofettaNicole Wong DooMark P. PurdueEleanor KaneGilles SallesGilles SallesBengt GlimeliusChristine F. SkibolaTongzhang ZhengGraham G. GilesGraham G. GilesScott DavisPierluigi CoccoKarin E. SmedbyMelissa C. SoutheyAlexandra NietersElizabeth A. HollyCorrado MagnaniPaul BrennanStephanie J. LaxDavid G. CoxLindsay M. MortonNikolaus BeckerQing LanElio RiboliHerve GhesquieresHerve GhesquieresRudolph KaaksJennifer J. TurnerMartha S. LinetAnne KrickerStephanie J. WeinsteinChristopher R. FlowersAlain MonnereauAlain MonnereauSilvia De SanjoséMary CarringtonJohn J. SpinelliPatricia HartgeNathaniel RothmanYolanda BenaventeSusan L. SlagerMartha GlennRichard K. SeversonOra PaltielYawei ZhangRuth C. TravisDemetrius AlbanesNicola J. CampPaige M. BracciJacqueline ClavelJacqueline ClavelJames R. CerhanMarc MaynadiéMaria Grazia EnnasMarie Hélène Delfau-laruePeter KraftHenrik HjalgrimRoger L. MilneRoger L. MilneAlan A. ArslanJacob MusinskyMartyn T. SmithAnthony StainesLauren R. TerasJenna M. VoutsinasLenka ForetovaSophia S. WangHans-olov AdamiAndrew L. FeldmanWendy CozenAngela Brooks-wilsonAngela Brooks-wilsonKenneth OffitBrian K. LinkBrenda M. BirmannSonja I. BerndtStephen J. ChanockJames MckayDennis D. WeisenburgerClaire M. VajdicGiancarlo LatteKaren CurtinW. Ryan DiverMads MelbyeMads MelbyeLucia CondeElizabeth E. BrownJoseph VijaiEve Roman

subject

Male0301 basic medicineHeterozygoteCancer Researchmedicine.medical_specialtySUSCEPTIBILITY LOCIChronic lymphocytic leukemiaEPIDEMIOLOGIC RESEARCHGenome-wide association studyHuman leukocyte antigenBiologyCLASSIFICATIONANTIGENSArticleGenetic Heterogeneity03 medical and health sciencesimmune system diseaseshemic and lymphatic diseasesInternal medicinemedicineINTERLYMPHHumans1112 Oncology and CarcinogenesisOncology & CarcinogenesisProspective StudiesGENOME-WIDE ASSOCIATIONAlleleHLA ComplexScience & TechnologyHematologyCHRONIC LYMPHOCYTIC-LEUKEMIAGenetic heterogeneityLymphoma Non-HodgkinHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHETEROZYGOTE ADVANTAGEmedicine.disease3. Good healthLymphoma030104 developmental biologyOncologyCase-Control StudiesImmunologyB-VIRUS INFECTIONFemaleLife Sciences & BiomedicineNEOPLASMSGenome-Wide Association Study

description

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.

yearjournalcountryeditionlanguage
2018-05-07Cancer Research
https://doi.org/10.1158/0008-5472.can-17-2900