A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Citation

McKay, James D.; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; & Lissowska, Jolanta, et al. (2011). A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium. PLOS Genetics, 7(3), e1001333. PMCID: PMC3060072

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.

URL

http://dx.doi.org/10.1371/journal.pgen.1001333

Reference Type

Journal Article

Year Published

2011

Journal Title

PLOS Genetics

Author(s)

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 M.
Wünsch-Filho, Victor
Eluf-Neto, José
Fernández Garrote, Leticia
Boccia, Stefania
Cadoni, Gabriella
Arzani, Dario
Olshan, Andrew F.
Weissler, Mark Christian
Funkhouser, William K.
Luo, Jingchun
Lubi
ński
, 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
Francheschi, 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 R.
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, José R.
Martinez, 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

PMCID

PMC3060072

ORCiD

Olshan - 0000-0001-9115-5128