A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
Abstract
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.
Type
Journal articleSubject
HumansHead and Neck Neoplasms
Genetic Predisposition to Disease
Aldehyde Dehydrogenase
Risk Factors
Gene Frequency
Adult
Aged
Middle Aged
Continental Population Groups
Female
Male
Genetic Variation
Genome-Wide Association Study
Biomarkers, Tumor
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https://hdl.handle.net/10161/17965Published Version (Please cite this version)
10.1371/journal.pgen.1001333Publication Info
McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun;
Byrnes, Graham; ... Brennan, Paul (2011). A genome-wide association study of upper aerodigestive tract cancers conducted within
the INHANCE consortium. PLoS genetics, 7(3). pp. e1001333. 10.1371/journal.pgen.1001333. Retrieved from https://hdl.handle.net/10161/17965.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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