A Meta-Analysis of Hodgkin Lymphoma Reveals 19p13.3 TCF3 as a Novel Susceptibility Locus

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  Cozen, W ; Timofeeva, MN ; Li, D ; Diepstra, A ; Hazelett, D ; Delahaye-Sourdeix, M ; Edlund, CK ; Franke, L ; Rostgaard, K ; Van Den Berg, DJ ; Cortessis, VK ; Smedby, KE ; Glaser, SL ; H-J, Westra ; Robison, LL ; Mack, TM ; Ghesquieres, H ; Hwang, AE ; Nieters, A ; de Sanjose, S ; Lightfoot, T ; Becker, N ; Maynadie, M ; Foretova, L ; Roman, E ; Benavente, Y ; Rand, KA ; Nathwani, BN ; Glimelius, B ; Staines, A ; Boffetta, P ; Link, BK ; Kiemeney, L ; Ansell, SM ; Bhatia, S ; Strong, LC ; Galan, P ; Vatten, L ; Habermann, TM ; Duell, EJ ; Lake, A ; Veenstra, RN ; Visser, L ; Liu, Y ; Urayama, KY ; Montgomery, D ; Gaborieau, V ; Weiss, LM ; Byrnes, G ; Lathrop, M ; Cocco, P ; Best, T ; Skol, AD ; H-O, Adami ; Melbye, M ; Cerhan, JR ; Gallagher, A ; Taylor, GM ; Slager, SL ; Brennan, P ; Coetzee, GA ; Conti, DV ; Onel, K ; Jarrett, RF ; Hjalgrim, H ; van den Berg, A ; McKay, JD
• Description:
  Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
• Subjects:
  Adolescent Adult Aged Aged, 80 And Over Basic Helix-Loop-Helix Transcription Factors Case-Control Studies Chromosomes, Human, Pair 19 Genetic Predisposition To Disease Genetic Variation Genome-Wide Association Study Hodgkin Disease Humans Male Middle Aged Young Adult

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• Source:
  Nat Commun. 5:3856
• Pubmed ID:
  24920014
• Pubmed Central ID:
  PMC4055950
• Document Type:
  Journal Article
• Funding:
  R01 CA136924/CA/NCI NIH HHSUnited States/ ; HD0433871/HD/NICHD NIH HHSUnited States/ ; R21 CA129045/CA/NCI NIH HHSUnited States/ ; R03 CA110836/CA/NCI NIH HHSUnited States/ ; R01CA136924/CA/NCI NIH HHSUnited States/ ; U58 DP000807/DP/NCCDPHP CDC HHSUnited States/ ; R01CA69269/CA/NCI NIH HHSUnited States/ ; CA097274/CA/NCI NIH HHSUnited States/ ; CA55727/CA/NCI NIH HHSUnited States/ ; P50 CA097274/CA/NCI NIH HHSUnited States/ ; CA129045/CA/NCI NIH HHSUnited States/ ; 001/WHO_/World Health OrganizationInternational/ ; N01PC35139/CA/NCI NIH HHSUnited States/ ; N01-PC-35136/PC/NCI NIH HHSUnited States/ ; R03CA110836/CA/NCI NIH HHSUnited States/ ; CA40046/CA/NCI NIH HHSUnited States/ ; U24 CA055727/CA/NCI NIH HHSUnited States/ ; P01 CA040046/CA/NCI NIH HHSUnited States/ ; N01-PC-35139/PC/NCI NIH HHSUnited States/ ; CA092153/CA/NCI NIH HHSUnited States/ ; 1U58DP000807-01/DP/NCCDPHP CDC HHSUnited States/ ; R01CA58839/CA/NCI NIH HHSUnited States/ ; R01 CA092153/CA/NCI NIH HHSUnited States/
• Volume:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:40a48d4a427e748da8f58b8e5616e6bbbef7da11c3b62ab10d33187a1d619a25
• Download URL:
  https://stacks.cdc.gov/view/cdc/27887/cdc_27887_DS1.pdf
• File Type:
  [PDF - 1.06 MB ]