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 Benhamou; Christine 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

doi:10.1371/journal.pgen.1001333

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 Benhamou

Christine 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

University at Buffalo, Stony Brook University

International Agency for Research on Cancer
Russian N.N. Blokhin Cancer Research Centre
Nofer Institute of Occupational Medicine
Maria Sklodowska-Curie Institute of Oncology
Hungarian National Institute of Environmental Health
Regional Authority of Public Health
Institute of Public Health
Charles University
Palacký University Olomouc
Masaryk Memorial Cancer Institute
National and Kapodistrian University of Athens
Harvard University
Institut national de la santé et de la recherche médicale
Institut Gustave Roussy
University of Geneva
University of Bremen
University of Turin
IRCCS Centro di Riferimento Oncologico - Aviano PN
General Hospital of Pordenone
Cancer Registry of Norway Institute of Population-Based Cancer Research
University of Aberdeen
University of Padua
Imperial College London
Institute Catala Oncologia
Centro de Investigación Biomédicaen Red de Epidemiología y Salud Pública (CIBERESP)
Newcastle University
University of Glasgow
University of Leeds
NHS National Services Scotland
Trinity College Dublin
Croatian National Institute of Public Health
Fundação Oswaldo Cruz
Universidade Federal de Pelotas
Universidade de São Paulo
National School of Public Health
Catholic University of the Sacred Heart
IRCCS San Raffaele Pisana - Roma
University of North Carolina at Chapel Hill
Pomeranian Medical University in Szczecin
Fred Hutchinson Cancer Research Center
Pennsylvania State University
University of California at Los Angeles
University of Texas MD Anderson Cancer Center
Instituto de Investigación Epidemiológica
Brown University
Boston University
University of Minnesota Twin Cities
University of Pittsburgh
Maastricht University
Radboud University Nijmegen
University of Toronto
Cancer Care Ontario
Norwegian University of Science and Technology
University of Tromsø – The Arctic University of Norway
University of Liverpool
Centro Per Lo Studio E La Prevenzione Oncologica
Civile-M.P.Arezzo Hospital
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
University of Naples Federico II
Bellvitge Biomedical Research Institute
Jefe Sección Información Sanitaria
Escuela Andaluza de Salud Publica
Murcia Regional Health Council
Instituto de Salud Publica, Pamplona
Subdirección de Salud Pública de Gipuzkoa
University of Cambridge
University of Oxford
National Institute of Public Health and the Environment
Utrecht University
Helmholtz Zentrum München - German Research Center for Environmental Health
German Cancer Research Center
German Institute of Human Nutrition Potsdam-Rehbruecke
Umeå University
Aarhus University
Danish Cancer Society
University Hospital of North Norway
University of Tartu
Centre National de Génotypage
CEPH-Fondation Jean Dausset
Université Paris 13
New York University
Blokhin Cancer Research Center
National Institute of Public Health
Charles University
National and Kapodistrian University of Athens
Harvard University
University of Paris Sud
Imperial College London
CIBER Epidemiología y Salud Pública (CIBERESP)
Universidade de São Paulo
Boston University
University of Toronto
University of Liverpool
Azienda Ospedaliera Civile M.P. Arezzo
University of Naples Federico II
IMIB-Arrixaca
University of Cambridge
University of Oxford
Institut Génomique, Commissariat À l'Énergie Atomique
Fondation Jean Dausset - CEPH
New York University

Research output: Contribution to journal › Article › peer-review

166 Scopus citations

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 language	English
Article number	e1001333
Journal	PLOS Genetics
Volume	7
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1001333
State	Published - Mar 2011

Access to Document

10.1371/journal.pgen.1001333

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), Article e1001333. https://doi.org/10.1371/journal.pgen.1001333

@article{89b2aed65112494386278236469317a6,

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

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.",

author = "McKay, \{James D.\} and Therese Truong and Valerie Gaborieau and Amelie Chabrier and Chuang, \{Shu Chun\} and Graham Byrnes and David Zaridze and Oxana Shangina and Neonila Szeszenia-Dabrowska and Jolanta Lissowska and Peter Rudnai and Eleonora Fabianova and Alexandru Bucur and Vladimir Bencko and Ivana Holcatova and Vladimir Janout and Lenka Foretova and Pagona Lagiou and Dimitrios Trichopoulos and Simone Benhamou and Christine Bouchardy and Wolfgang Ahrens and Franco Merletti and Lorenzo Richiardi and Renato Talamini and Luigi Barzan and Kristina Kjaerheim and Macfarlane, \{Gary J.\} and Macfarlane, \{Tatiana V.\} and Lorenzo Simonato and Cristina Canova and Antonio Agudo and Xavier Castellsagu{\'e} and Ray Lowry and Conway, \{David I.\} and McKinney, \{Patricia A.\} and Healy, \{Claire M.\} and Toner, \{Mary E.\} and Ariana Znaor and Curado, \{Maria Paula\} and Sergio Koifman and Ana Menezes and Victor W{\"u}nsch-Filho and Neto, \{Jos{\'e} Eluf\} and Garrote, \{Leticia Fern{\'a}ndez\} and Stefania Boccia and Gabriella Cadoni and Dario Arzani and Olshan, \{Andrew F.\} and Weissler, \{Mark C.\} and Funkhouser, \{William K.\} and Jingchun Luo and Jan Lubi{\'n}ski and Joanna Trubicka and Marcin Lener and Dorota Oszutowska and Schwartz, \{Stephen M.\} and Chu Chen and Sherianne Fish and Doody, \{David R.\} and Muscat, \{Joshua E.\} and Philip Lazarus and Gallagher, \{Carla J.\} and Chang, \{Shen Chih\} and Zhang, \{Zuo Feng\} and Qingyi Wei and Sturgis, \{Erich M.\} and Wang, \{Li E.\} and Silvia Franceschi and Rolando Herrero and Kelsey, \{Karl T.\} and McClean, \{Michael D.\} and Marsit, \{Carmen J.\} and Nelson, \{Heather H.\} and Marjorie Romkes and Shama Buch and Tomoko Nukui and Shilong Zhong and Martin Lacko and Manni, \{Johannes J.\} and Peters, \{Wilbert H.M.\} and Hung, \{Rayjean J.\} and John McLaughlin and Lars Vatten and Inger Nj{\o}lstad and Goodman, \{Gary E.\} and Field, \{John K.\} and Triantafillos Liloglou and Paolo Vineis and Francoise Clavel-Chapelon and Domenico Palli and Rosario Tumino and Vittorio Krogh and Salvatore Panico and Gonz{\'a}lez, \{Carlos A.\} and Quir{\'o}s, \{J. Ram{\'o}n\} and Carmen Mart{\'i}nez and Carmen Navarro and Eva Ardanaz and Nerea Larra{\~n}aga and Khaw, \{Kay Tee\} and Timothy Key and Bueno-de-Mesquita, \{H. Bas\} and Peeters, \{Petra H.M.\} and Antonia Trichopoulou and Jakob Linseisen and Heiner Boeing and G{\"o}ran Hallmans and Kim Overvad and Anne Tj{\o}nneland and Merethe Kumle and Elio Riboli and Kristjan V{\"a}lk and T{\~o}nu Voodern and Andres Metspalu and Diana Zelenika and Anne Boland and Marc Delepine and Mario Foglio and Doris Lechner and H{\'e}l{\`e}ne Blanch{\'e} and Gut, \{Ivo G.\} and Pilar Galan and Simon Heath and Mia Hashibe and Hayes, \{Richard B.\} and Paolo Boffetta and Mark Lathrop and Paul Brennan",

year = "2011",

month = mar,

doi = "10.1371/journal.pgen.1001333",

language = "English",

volume = "7",

journal = "PLOS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "3",

}

McKay, JD, Truong, T, Gaborieau, V, Chabrier, A, Chuang, SC, 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, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, GJ, Macfarlane, TV, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, DI, McKinney, PA, Healy, CM, Toner, ME, Znaor, A, Curado, MP, Koifman, S, Menezes, A, Wünsch-Filho, V, Neto, JE, Garrote, LF, Boccia, S, Cadoni, G, Arzani, D, Olshan, AF, Weissler, MC, Funkhouser, WK, Luo, J, Lubiński, J, Trubicka, J, Lener, M, Oszutowska, D, Schwartz, SM, Chen, C, Fish, S, Doody, DR, Muscat, JE, Lazarus, P, Gallagher, CJ, Chang, SC, Zhang, ZF, Wei, Q, Sturgis, EM, Wang, LE, Franceschi, S, Herrero, R, Kelsey, KT, McClean, MD, Marsit, CJ, Nelson, HH, Romkes, M, Buch, S, Nukui, T, Zhong, S, Lacko, M, Manni, JJ, Peters, WHM, Hung, RJ, McLaughlin, J, Vatten, L, Njølstad, I, Goodman, GE, Field, JK, Liloglou, T, Vineis, P, Clavel-Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, S, González, CA, Quirós, JR, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, Khaw, KT, Key, T, Bueno-de-Mesquita, HB, Peeters, PHM, Trichopoulou, A, Linseisen, J, Boeing, H, Hallmans, G, Overvad, K, Tjønneland, A, Kumle, M, Riboli, E, Välk, K, Voodern, T, Metspalu, A, Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Blanché, H, Gut, IG, Galan, P, Heath, S, Hashibe, M, Hayes, RB, Boffetta, P, Lathrop, M & Brennan, P 2011, 'A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium', PLOS Genetics, vol. 7, no. 3, e1001333. https://doi.org/10.1371/journal.pgen.1001333

TY - JOUR

T1 - A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

AU - McKay, James D.

AU - Truong, Therese

AU - Gaborieau, Valerie

AU - Chabrier, Amelie

AU - Chuang, Shu Chun

AU - Byrnes, Graham

AU - Zaridze, David

AU - Shangina, Oxana

AU - Szeszenia-Dabrowska, Neonila

AU - Lissowska, Jolanta

AU - Rudnai, Peter

AU - Fabianova, Eleonora

AU - Bucur, Alexandru

AU - Bencko, Vladimir

AU - Holcatova, Ivana

AU - Janout, Vladimir

AU - Foretova, Lenka

AU - Lagiou, Pagona

AU - Trichopoulos, Dimitrios

AU - Benhamou, Simone

AU - Bouchardy, Christine

AU - Ahrens, Wolfgang

AU - Merletti, Franco

AU - Richiardi, Lorenzo

AU - Talamini, Renato

AU - Barzan, Luigi

AU - Kjaerheim, Kristina

AU - Macfarlane, Gary J.

AU - Macfarlane, Tatiana V.

AU - Simonato, Lorenzo

AU - Canova, Cristina

AU - Agudo, Antonio

AU - Castellsagué, Xavier

AU - Lowry, Ray

AU - Conway, David I.

AU - McKinney, Patricia A.

AU - Healy, Claire M.

AU - Toner, Mary E.

AU - Znaor, Ariana

AU - Curado, Maria Paula

AU - Koifman, Sergio

AU - Menezes, Ana

AU - Wünsch-Filho, Victor

AU - Neto, José Eluf

AU - Garrote, Leticia Fernández

AU - Boccia, Stefania

AU - Cadoni, Gabriella

AU - Arzani, Dario

AU - Olshan, Andrew F.

AU - Weissler, Mark C.

AU - Funkhouser, William K.

AU - Luo, Jingchun

AU - Lubiński, Jan

AU - Trubicka, Joanna

AU - Lener, Marcin

AU - Oszutowska, Dorota

AU - Schwartz, Stephen M.

AU - Chen, Chu

AU - Fish, Sherianne

AU - Doody, David R.

AU - Muscat, Joshua E.

AU - Lazarus, Philip

AU - Gallagher, Carla J.

AU - Chang, Shen Chih

AU - Zhang, Zuo Feng

AU - Wei, Qingyi

AU - Sturgis, Erich M.

AU - Wang, Li E.

AU - Franceschi, Silvia

AU - Herrero, Rolando

AU - Kelsey, Karl T.

AU - McClean, Michael D.

AU - Marsit, Carmen J.

AU - Nelson, Heather H.

AU - Romkes, Marjorie

AU - Buch, Shama

AU - Nukui, Tomoko

AU - Zhong, Shilong

AU - Lacko, Martin

AU - Manni, Johannes J.

AU - Peters, Wilbert H.M.

AU - Hung, Rayjean J.

AU - McLaughlin, John

AU - Vatten, Lars

AU - Njølstad, Inger

AU - Goodman, Gary E.

AU - Field, John K.

AU - Liloglou, Triantafillos

AU - Vineis, Paolo

AU - Clavel-Chapelon, Francoise

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Krogh, Vittorio

AU - Panico, Salvatore

AU - González, Carlos A.

AU - Quirós, J. Ramón

AU - Martínez, Carmen

AU - Navarro, Carmen

AU - Ardanaz, Eva

AU - Larrañaga, Nerea

AU - Khaw, Kay Tee

AU - Key, Timothy

AU - Bueno-de-Mesquita, H. Bas

AU - Peeters, Petra H.M.

AU - Trichopoulou, Antonia

AU - Linseisen, Jakob

AU - Boeing, Heiner

AU - Hallmans, Göran

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Kumle, Merethe

AU - Riboli, Elio

AU - Välk, Kristjan

AU - Voodern, Tõnu

AU - Metspalu, Andres

AU - Zelenika, Diana

AU - Boland, Anne

AU - Delepine, Marc

AU - Foglio, Mario

AU - Lechner, Doris

AU - Blanché, Hélène

AU - Gut, Ivo G.

AU - Galan, Pilar

AU - Heath, Simon

AU - Hashibe, Mia

AU - Hayes, Richard B.

AU - Boffetta, Paolo

AU - Lathrop, Mark

AU - Brennan, Paul

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/79953761295

U2 - 10.1371/journal.pgen.1001333

DO - 10.1371/journal.pgen.1001333

M3 - Article

C2 - 21437268

SN - 1553-7390

VL - 7

JO - PLOS Genetics

JF - PLOS Genetics

IS - 3

M1 - e1001333

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this