HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

Details

• Alternative Title:
  Cancer Res
• Personal Author:
  Wang, Sophia S. ; Carrington, Mary ; Berndt, Sonja I. ; Slager, Susan L. ; Bracci, Paige M. ; Voutsinas, Jenna ; Cerhan, James R. ; Smedby, Karin E. ; Hjalgrim, Henrik ; Vijai, Joseph ; Morton, Lindsay M. ; Vermeulen, Roel ; Paltiel, Ora ; Vajdic, Claire M. ; Linet, Martha S. ; Nieters, Alexandra ; de Sanjose, 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, Rudolph ; Riboli, Elio ; Benavente, Yolanda ; Brennan, Paul ; McKay, James ; Delfau-Larue, Marie-Hélène ; Link, Brian K. ; Magnani, Corrado ; Ennas, Maria Grazia ; Latte, Giancarlo ; Feldman, Andrew L. ; Doo, Nicole Wong ; Giles, Graham G. ; Southey, Melissa C. ; Milne, Roger L. ; Offit, Kenneth ; Musinsky, Jacob ; Arslan, Alan A. ; Purdue, Mark P. ; Adami, Hans-Olov ; Melbye, Mads ; Glimelius, Bengt ; Conde, Lucia ; Camp, Nicola J. ; Glenn, Martha ; Curtin, Karen ; Clavel, Jacqueline ; Monnereau, Alain ; Cox, David G. ; Ghesquières, Hervé ; Salles, Gilles ; Bofetta, Paulo ; Foretova, Lenka ; Staines, Anthony ; Davis, Scott ; Severson, Richard K. ; Lan, Qing ; Brooks-Wilson, Angela ; Smith, Martyn T ; Roman, Eve ; Kricker, Anne ; Zhang, Yawei ; Kraft, Peter ; Chanock, Stephen J. ; Rothman, Nathaniel ; Hartge, Patricia ; Skibola, Christine F.
• Description:
  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 (| 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.| HLA gene diversity reduces risk for non-Hodgkin lymphoma. |.
• Subjects:
  Article
• Source:
  Cancer Res. 78(14):4086-4096
• Pubmed ID:
  29735552
• Pubmed Central ID:
  PMC6065509
• Document Type:
  Journal Article
• Funding:
  N01 PC067009/CN/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; HHSN261201000140C/CA/NCI NIH HHS/United States ; N01 PC067010/PC/NCI NIH HHS/United States ; R01 CA098122/CA/NCI NIH HHS/United States ; U01 HG007033/HG/NHGRI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; HHSN261201000035C/CA/NCI NIH HHS/United States ; R21 CA165923/CA/NCI NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; N01 PC067008/PC/NCI NIH HHS/United States ; R01 CA148690/CA/NCI NIH HHS/United States ; N01 PC065064/PC/WHI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; U58 DP000807/DP/NCCDPHP CDC HHS/United States ; R01 CA154643/CA/NCI NIH HHS/United States ; R01 CA062006/CA/NCI NIH HHS/United States ; K08 CA134919/CA/NCI NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; R01 CA098661/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 CA092153/CA/NCI NIH HHS/United States ; HHSN261201000035I/CA/NCI NIH HHS/United States ; HHSN261201000034C/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; HHSN261201500005C/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; P50 CA097274/CA/NCI NIH HHS/United States ; R01 CA049449/CA/NCI NIH HHS/United States ; R01 CA200703/CA/NCI NIH HHS/United States ; N01CO12400/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; U01 CA049449/CA/NCI NIH HHS/United States ; R03 CA179558/CA/NCI NIH HHS/United States ; R01 CA149445/CA/NCI NIH HHS/United States ; R01 CA134674/CA/NCI NIH HHS/United States ; HHSN261201000026C/CA/NCI NIH HHS/United States ; U01 CA118444/CA/NCI NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States
• Volume:
  78
• Issue:
  14
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:7835deabfac204273c3c0c2f040958058944dfab8b96164a712f92dccb969134
• Download URL:
  https://stacks.cdc.gov/view/cdc/57779/cdc_57779_DS1.pdf
• File Type:
  [PDF - 153.36 KB ]