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

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

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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.

Original languageEnglish (US)
Article numbere1001333
JournalPLoS genetics
Volume7
Issue number3
DOIs
StatePublished - Mar 2011

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All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

McKay, J. D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S. C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., ... Brennan, P. (2011). A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS genetics, 7(3), [e1001333]. https://doi.org/10.1371/journal.pgen.1001333