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

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Date
2011-03-17
Authors
McKay, James D
Truong, Therese
Gaborieau, Valerie
Chabrier, Amelie
Chuang, Shu-Chun
Byrnes, Graham
Zaridze, David
Shangina, Oxana
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Bucur, Alexandru
Bencko, Vladimir
Holcatova, Ivana
Janout, Vladimir
Foretova, Lenka
Lagiou, Pagona
Trichopoulos, Dimitrios
Benhamou, Simone
Bouchardy, Christine
Ahrens, Wolfgang
Merletti, Franco
Richiardi, Lorenzo
Talamini, Renato
Barzan, Luigi
Kjaerheim, Kristina
Macfarlane, Gary J
Macfarlane, Tatiana V
Simonato, Lorenzo
Canova, Cristina
Agudo, Antonio
Castellsagué, Xavier
Lowry, Ray
Conway, David I
McKinney, Patricia A
Healy, Claire M
Healy, Claire M
Toner, Mary E
Znaor, Ariana
Curado, Maria Paula
Koifman, Sergio
Menezes, Ana
Wünsch-Filho, Victor
Neto, José Eluf
Garrote, Leticia Fernández
Boccia, Stefania
Cadoni, Gabriella
Arzani, Dario
Olshan, Andrew F
Weissler, Mark C
Funkhouser, William K
Luo, Jingchun
Lubiński, Jan
Trubicka, Joanna
Lener, Marcin
Oszutowska, Dorota
Schwartz, Stephen M
Chen, Chu
Fish, Sherianne
Doody, David R
Muscat, Joshua E
Lazarus, Philip
Gallagher, Carla J
Chang, Shen-Chih
Zhang, Zuo-Feng
Wei, Qingyi
Sturgis, Erich M
Wang, Li-E
Franceschi, Silvia
Herrero, Rolando
Kelsey, Karl T
McClean, Michael D
Marsit, Carmen J
Nelson, Heather H
Romkes, Marjorie
Buch, Shama
Nukui, Tomoko
Zhong, Shilong
Lacko, Martin
Manni, Johannes J
Peters, Wilbert HM
Hung, Rayjean J
McLaughlin, John
Vatten, Lars
Njølstad, Inger
Goodman, Gary E
Field, John K
Liloglou, Triantafillos
Vineis, Paolo
Clavel-Chapelon, Francoise
Palli, Domenico
Tumino, Rosario
Krogh, Vittorio
Panico, Salvatore
González, Carlos A
Quirós, J Ramón
Martínez, Carmen
Navarro, Carmen
Ardanaz, Eva
Larrañaga, Nerea
Khaw, Kay-Tee
Key, Timothy
Bueno-de-Mesquita, H Bas
Peeters, Petra HM
Trichopoulou, Antonia
Linseisen, Jakob
Boeing, Heiner
Hallmans, Göran
Overvad, Kim
Tjønneland, Anne
Kumle, Merethe
Riboli, Elio
Välk, Kristjan
Vooder, Tõnu
Metspalu, Andres
Zelenika, Diana
Boland, Anne
Delepine, Marc
Foglio, Mario
Lechner, Doris
Blanché, Hélène
Gut, Ivo G
Galan, Pilar
Heath, Simon
Hashibe, Mia
Hayes, Richard B
Boffetta, Paolo
Lathrop, Mark
Brennan, Paul
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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 article
Subject
Humans
Head 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
Permalink
https://hdl.handle.net/10161/17965
Published Version (Please cite this version)
10.1371/journal.pgen.1001333
Publication 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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Scholars@Duke

Wei

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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