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

McKay, James D
; 
Truong, Therese
; 
Gaborieau, Valerie
; 
Chabrier, Amelie
; 
Chuang, Shu-Chun
; 
Byrnes, Graham
; 
Zaridze, David
; 
Shangina, Oxana
; 
Szeszenia-Dabrowska, Neonila
; 
Lissowska, Jolanta
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Author
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
 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 H M
 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 H M
 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
Advisors
Editors
Other Contributors
Departments
International Agency for Research on Cancer (IARC), Lyon, France.
Date
2011-03
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adult
Aged
Aldehyde Dehydrogenase
Continental Population Groups
Female
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Head and Neck Neoplasms
Humans
Male
Middle Aged
Risk Factors
Tumor Markers, Biological
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/221851
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.
Language
en
Citation
A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. 2011, 7 (3):e1001333 PLoS Genet.
ISSN
1553-7404
eISSN
ISBN
DOI
10.1371/journal.pgen.1001333
PMID
21437268
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval
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