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 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 Vooder, 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

Research output: Contribution to journalArticle

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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
Article numbere1001333
Number of pages13
JournalPLoS Genetics
Volume7
Issue number3
DOIs
Publication statusPublished - 17 Mar 2011

Fingerprint

Genome-Wide Association Study
digestive tract
Gastrointestinal Tract
cancer
genome
neoplasms
Neoplasms
gene
Abraxas
Genes
genetic variation
genes
aldehyde dehydrogenase
Aldehyde Dehydrogenase
genome-wide association study
Linkage Disequilibrium
Multigene Family
aldehyde
linkage disequilibrium
DNA repair

Keywords

  • 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

Cite this

McKay, J. D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S-C., Byrnes, G., ... 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

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; 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; 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; Voodern, 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.

In: PLoS Genetics, Vol. 7, No. 3, e1001333, 17.03.2011.

Research output: Contribution to journalArticle

McKay, JD, 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, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, GJ, MacFarlane, T, 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, S-C, Zhang, Z-F, Wei, Q, Sturgis, EM, Wang, L-E, 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, K-T, 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, Vooder, T, 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
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 ; 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 ; Voodern, 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. / A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. In: PLoS Genetics. 2011 ; Vol. 7, No. 3.
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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.",
keywords = "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",
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month = "3",
day = "17",
doi = "10.1371/journal.pgen.1001333",
language = "English",
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journal = "PLoS Genetics",
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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

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 - Vooder, Tõnu

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 - 2011/3/17

Y1 - 2011/3/17

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.

KW - Adult

KW - Aged

KW - Aldehyde Dehydrogenase

KW - Continental Population Groups

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Head and Neck Neoplasms

KW - Humans

KW - Male

KW - Middle Aged

KW - Risk Factors

KW - Tumor Markers, Biological

U2 - 10.1371/journal.pgen.1001333

DO - 10.1371/journal.pgen.1001333

M3 - Article

C2 - 21437268

VL - 7

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 3

M1 - e1001333

ER -