HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes
Publication date
2018-07
Authors
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
Editors
Advisors
Supervisors
Document Type
Article
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taverne
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
Keywords
Taverne, SDG 3 - Good Health and Well-being
Citation
Wang, S S, Carrington, M, Berndt, S I, Slager, S L, Bracci, P M, Voutsinas, J, Cerhan, J R, Ekström Smedby, K, Hjalgrim, H, Vijai, J, Morton, L M, Vermeulen, R, Paltiel, O, Vajdic, C M, Linet, M S, Nieters, A, de Sanjosé, 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 D, Delfau-Larue, M H, Link, B K, Magnani, C, Ennas, M G, Latte, G, Feldman, A L, Wong Doo, N, Giles, G G & Southey, M C 2018, 'HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes', Cancer Research, vol. 78, no. 14, pp. 4086-4096. https://doi.org/10.1158/0008-5472.CAN-17-2900