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CC BY V4.0, Open Access
Journal article
A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
PLoS genetics, Vol.7(3), pp.e1001333-e1001333
2011
Handle:
https://hdl.handle.net/2376/114171
PMCID: PMC3060072
PMID: 21437268
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 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 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 x 10(-8); rs1229984-ADH1B, p = 7 x 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.
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- Title
- A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- Creators
- James D McKay - International Agency for Research on CancerPhilip Lazarus - Penn State College of Medicine- Therese Truong - International Agency for Research on CancerValerie Gaborieau - International Agency for Research on CancerAmélie Chabrier - International Agency for Research on CancerShu-Chun Chuang - International Agency for Research on CancerGraham BYRNES - International Agency for Research on CancerDavid Zaridze - Russian Academy of Medical SciencesOxana Shangina - Russian Academy of Medical SciencesNeonila Szeszenia-Dabrowska - Department of EpidemiologyJolanta Lissowska - Maria Skłodowska Curie Memorial Cancer CenterPeter Rudnai - National Institute for EnvironmentEleonora Fabianova - Regional Authority of Public HealthAlexandru Bucur - Institute of Public HealthVladimir Bencko - Charles University in PragueIvana Holcatova - Charles University in PragueVladimir Janout - Palacky University OlomoucLenka Foretova - Department of Cancer Epidemiology and GeneticsPagona Lagiou - National and Kapodistrian University of AthensDimitrios Trichopoulos - National and Kapodistrian University of AthensSimone Benhamou - Variabilité Génétique et Maladies HumainesChristine Bouchardy - Université de GenèveWolfgang Ahrens - Bremen Institute for Prevention Research and Social Medicine (BIPS)Franco Merletti - Universita di TorinoLorenzo Richiardi - Universita di TorinoRenato Talamini - Istituto di Ricovero e Cura a Carattere ScientificoLuigi Barzan - General HospitalKristina Kjaerheim - Cancer Registry of NorwayGary J Macfarlane - School of Medicine and DentistryTatiana V Macfarlane - School of Medicine and DentistryLorenzo Simonato - Universita di PadovaCristina Canova - Universita di PadovaAntonio Agudo - Catalan Institute of OncologyXavier Castellsagué - Catalan Institute of OncologyRay Lowry - Newcastle University [Newcastle]David I Conway - Dental SchoolPatricia A McKinney - Centre for Epidemiology and BiostatisticsClaire M Healy - School of Dental ScienceMary E Toner - School of Dental ScienceAriana Znaor - National Institute of Public HealthMaria Paula Curado - International Agency for Research on CancerSergio Koifman - National School of Public HealthAna Menezes - Universidade Federal de Pelotas = Federal University of PelotasVictor Wüensch-Filho - Universidade de São PauloJosé Eluf Neto - Universidade de São PauloLeticia Fernandez Garrote - Institute of Oncology and RadiobiologyStefania Boccia - Università Cattolica del Sacro CuoreGabriella Cadoni - Institute of HygieneDario Arzani - Institute of HygieneAndrew F Olshan - University of North CarolinaMark C Weissler - University of North CarolinaWilliam K Funkhouser - University of North CarolinaJingchun Luo - University of North CarolinaJan Lubinski - Pomeranian Medical UniversityJoanna Trubicka - Pomeranian Medical UniversityMarcin Lener - Pomeranian Medical UniversityDorota Oszutowska - Pomeranian Medical UniversityStephen M Schwartz - Fred Hutchinson Cancer Research Center [Seattle]Chu Chen - Fred Hutchinson Cancer Research Center [Seattle]Sherianne Fish - Fred Hutchinson Cancer Research Center [Seattle]David R Doody - Fred Hutchinson Cancer Research Center [Seattle]Joshua E Muscat - Penn State College of MedicineCarla J Gallagher - Penn State College of MedicineShen-Chih Chang - University of California [Los Angeles]Zuo-Feng Zhang - University of California [Los Angeles]Qingyi Wei - Anderson Cancer CenterErich M Sturgis - Anderson Cancer CenterLi-E Wang - Anderson Cancer CenterSilvia Franceschi - International Agency for Research on CancerRolando Herrero - Instituto de Investigación EpidemiológicaKarl T Kelsey - Brown UniversityMichael D McClean - School of public healthCarmen J Marsit - Brown UniversityHeather H Nelson - Masonic Cancer CenterMarjorie Romkes - University of PittsburghShama Buch - University of PittsburghTomoko Nukui - University of PittsburghShilong Zhong - University of PittsburghMartin Lacko - Maastricht University [Maastricht]Johannes J Manni - Maastricht University [Maastricht]Wilbert H. M Peters - Radboud University Medical Center [Nijmegen]Rayjean J Hung - Mount Sinai Hospital [Toronto, Canada]John Mclaughlin - Cancer Care OntarioLars Vatten - Norwegian University of Science and TechnologyInger Njolstad - University of TromsøGary E Goodman - Fred Hutchinson Cancer Research Center [Seattle]John K Field - University of LiverpoolTriantafillos Liloglou - University of LiverpoolPaolo Vineis - Piedmont Reference Center for Epidemiology and Cancer PreventionFrançoise Clavel-Chapelon - Institut National de la Santé et de la Recherche MédicaleDomenico Palli - Istituto per lo Studio e la Prevezione OncologicaRosario Tumino - Civile - M.P.Arezzo HospitalVittorio Krogh - Istituto di Ricovero e Cura a Carattere ScientificoSalvatore Panico - Department of Clinical and Experimental MedicineCarlos A GonzalezJ Ramon QuirósCarmen MartinezCarmen NavarroEva ArdanazNerea Larrañaga
- Publication Details
- PLoS genetics, Vol.7(3), pp.e1001333-e1001333
- Academic Unit
- Department of Pharmaceutical Sciences
- Publisher
- Public Library of Science
- Identifiers
- 99900547841201842
- Language
- English
- Resource Type
- Journal article