HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes
Wang, Sophia S.; Carrington, Mary; Berndt, Sonja I.; Slager, Susan L.; Bracci, Paige M.; Voutsinas, Jenna; Cerhan, James R.; Ekström Smedby, Karin; Hjalgrim, Henrik; Vijai, Joseph; Morton, Lindsay M.; Vermeulen, Roel; Paltiel, Ora; Vajdic, Claire M; Linet, Martha S.; Nieters, Alexandra; de Sanjosé, Silvia; Cozen, Wendy; Brown, Elizabeth E.; Turner, Jennifer; Spinelli, John J.; Zheng, Tongzhang; Birmann, Brenda M.; Flowers, Christopher R.; Becker, Nikolaus; Holly, Elizabeth A.; Kane, Eleanor; Weisenburger, Dennis; Maynadie, Marc; Cocco, Pierluigi; Albanes, Demetrius; Weinstein, Stephanie J.; Teras, Lauren R.; Diver, W. Ryan; Lax, Stephanie J.; Travis, Ruth C.; Kaaks, Rudolf; Riboli, Elio; Benavente, Yolanda; Brennan, Paul; McKay, James D.; Delfau-Larue, Marie Helene; Link, Brian K; Magnani, Corrado; Ennas, Maria G; Latte, Giancarlo; Feldman, Andrew L; Wong Doo, Nicole; Giles, Graham G.; Southey, Melissa C.
(2018) Cancer Research, volume 78, issue 14, pp. 4086 - 4096
(Article)
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
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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
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Keywords: Taverne
ISSN: 0008-5472
Publisher: American Association for Cancer Research Inc.
(Peer reviewed)
