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A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Contributeurs/tricesMcKay, James D; INHANCE Consortium
Publié dansPLOS genetics, vol. 7, no. 3, e1001333
Date de publication2011
Résumé

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Mots-clés
  • Adult
  • Aged
  • Aldehyde Dehydrogenase/genetics
  • Continental Population Groups
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Head and Neck Neoplasms/enzymology/epidemiology/genetics
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Tumor Markers, Biological/genetics
Citation (format ISO)
MCKAY, James D. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. In: PLOS genetics, 2011, vol. 7, n° 3, p. e1001333. doi: 10.1371/journal.pgen.1001333
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Article (Published version)
Identifiants
ISSN du journal1553-7390
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Informations techniques

Création20.11.2012 15:20:00
Première validation20.11.2012 15:20:00
Heure de mise à jour14.03.2023 17:47:26
Changement de statut14.03.2023 17:47:26
Dernière indexation12.02.2024 11:16:38
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