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

Stefania Boccia; 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; 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.

Stefania Boccia, 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 TrichopoulosSimone 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, 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

Risultato della ricerca: Contributo in rivista › Articolo in rivista

132 Citazioni (Scopus)

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.

Lingua originale	English
pagine (da-a)	e1001333-e1001333
Numero di pagine	13
Rivista	PLoS Genetics
DOI	https://doi.org/10.1371/journal.pgen.1001333
Stato di pubblicazione	Pubblicato - 2011

Keywords

cancers
genome-wide

Accesso al documento

10.1371/journal.pgen.1001333

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Cita questo

Boccia, S., 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., ... Brennan, P. (2011). A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genetics, e1001333-e1001333. https://doi.org/10.1371/journal.pgen.1001333

Boccia, Stefania ; 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 ; Wünsch-Filho, Victor ; Neto, José Eluf ; Garrote, Leticia Fernández ; 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 ; 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 ; pagg. e1001333-e1001333.

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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.",

keywords = "cancers, genome-wide, cancers, genome-wide",

author = "Stefania Boccia and Mckay, {James D.} and Therese Truong and Valerie Gaborieau and Amelie Chabrier and Shu-Chun Chuang 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 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 Shen-Chih Chang and Zuo-Feng Zhang and Qingyi Wei and Sturgis, {Erich M.} and Li-E Wang 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 Kay-Tee Khaw 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",

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

language = "English",

pages = "e1001333--e1001333",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "San Francisco, CA : Public Library of Science, c2005-",

}

Boccia, S, 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, 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, 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, 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, pagg. e1001333-e1001333. https://doi.org/10.1371/journal.pgen.1001333

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. / Boccia, Stefania; 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; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; 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; 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, 2011, pag. e1001333-e1001333.

Risultato della ricerca: Contributo in rivista › Articolo in rivista

TY - JOUR

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

AU - Boccia, Stefania

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 - 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

Y1 - 2011

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 - cancers

KW - genome-wide

KW - cancers

KW - genome-wide

UR - http://hdl.handle.net/10807/3561

U2 - 10.1371/journal.pgen.1001333

DO - 10.1371/journal.pgen.1001333

M3 - Article

SP - e1001333-e1001333

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

ER -