| Literature DB >> 29735552 |
Sophia S Wang1, Mary Carrington2, Sonja I Berndt3, Susan L Slager4, Paige M Bracci5, Jenna Voutsinas6, James R Cerhan4, Karin E Smedby7,8, Henrik Hjalgrim9,10, Joseph Vijai11, Lindsay M Morton3, Roel Vermeulen12,13, Ora Paltiel14, Claire M Vajdic15, Martha S Linet3, Alexandra Nieters16, Silvia de Sanjose17,18, Wendy Cozen19, Elizabeth E Brown20, Jennifer Turner21,22, John J Spinelli23,24, Tongzhang Zheng25, Brenda M Birmann26, Christopher R Flowers27, Nikolaus Becker28, Elizabeth A Holly5, Eleanor Kane29, Dennis Weisenburger30, Marc Maynadie31, Pierluigi Cocco32, Demetrius Albanes3, Stephanie J Weinstein3, Lauren R Teras33, W Ryan Diver33, Stephanie J Lax29, Ruth C Travis34, Rudolph Kaaks28, Elio Riboli35, Yolanda Benavente17,18, Paul Brennan36, James McKay37, Marie-Hélène Delfau-Larue37,38, Brian K Link39, Corrado Magnani40, Maria Grazia Ennas41, Giancarlo Latte42, Andrew L Feldman43, Nicole Wong Doo44, Graham G Giles44,45, Melissa C Southey46, Roger L Milne44,45, Kenneth Offit10, Jacob Musinsky10, Alan A Arslan47,48,49, Mark P Purdue3, Hans-Olov Adami50, Mads Melbye9,51, Bengt Glimelius52, Lucia Conde53, Nicola J Camp54, Martha Glenn54, Karen Curtin54, Jacqueline Clavel55,56, Alain Monnereau56,56,57, David G Cox58, Hervé Ghesquières56,59, Gilles Salles59,60, Paulo Bofetta61, Lenka Foretova62, Anthony Staines63, Scott Davis64, Richard K Severson65, Qing Lan3, Angela Brooks-Wilson66,67, Martyn T Smith68, Eve Roman29, Anne Kricker69, Yawei Zhang70,71, Peter Kraft72,73, Stephen J Chanock3, Nathaniel Rothman3, Patricia Hartge3, Christine F Skibola27.
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. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 29735552 PMCID： PMC6065509 DOI： 10.1158/0008-5472.CAN-17-2900
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 13.312