Peer-Reviewed Journal Details
Mandatory Fields
Wang, SS;Carrington, M;Berndt, SI;Slager, SL;Bracci, PM;Voutsinas, J;Cerhan, JR;Smedby, KE;Hjalgrim, H;Vijai, J;Morton, LM;Vermeulen, R;Paltiel, O;Vajdic, CM;Linet, MS;Nieters, A;de Sanjose, S;Cozen, W;Brown, EE;Turner, J;Spinelli, JJ;Zheng, TZ;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, J;Delfau-Larue, MH;Link, BK;Magnani, C;Ennas, MG;Latte, G;Feldman, AL;Doo, NW;Giles, GG;Southey, MC;Milne, RL;Offit, K;Musinsky, 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;Ghesquieres, H;Salles, G;Bofetta, P;Foretova, L;Staines, A;Davis, S;Severson, RK;Lan, Q;Brooks-Wilson, A;Smith, MT;Roman, E;Kricker, A;Zhang, YW;Kraft, P;Chanock, SJ;Rothman, N;Hartge, P;Skibola, CF
2018
July
Cancer Research
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Published
2 ()
Optional Fields
GENOME-WIDE ASSOCIATION CHRONIC LYMPHOCYTIC-LEUKEMIA B-VIRUS INFECTION HETEROZYGOTE ADVANTAGE EPIDEMIOLOGIC RESEARCH SUSCEPTIBILITY LOCI CLASSIFICATION INTERLYMPH NEOPLASMS ANTIGENS
78
4086
4096
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. (C) 2018 AACR.
PHILADELPHIA
0008-5472
10.1158/0008-5472.CAN-17-2900
Grant Details