A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Date publication

juin 2014

Journal

Nature communications

Auteurs

Membres identifiés du Cancéropôle Est :
Pr MAYNADIE Marc

Tous les auteurs :
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, Westra HJ, 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, Adami HO, 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

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/24920014

Résumé

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.

Mots clés

Adolescent, Adult, Aged, Aged, 80 and over, Basic Helix-Loop-Helix Transcription Factors, genetics, Case-Control Studies, Chromosomes, Human, Pair 19, genetics, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Hodgkin Disease, genetics, Humans, Male, Middle Aged, Young Adult

Référence

Nat Commun. 2014 Jun;5:3856