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

McKay, JD and Truong, T and Gaborieau, V and Chabrier, A and Chuang, SC and Byrnes, G and Zaridze, D and Shangina, O and Szeszenia-Dabrowska, N and Lissowska, J and Rudnai, P and Fabianova, E and Bucur, A and Bencko, V and Holcatova, I and Janout, V and Foretova, L and Lagiou, P and Trichopoulos, D and Benhamou, S and Bouchardy, C and Ahrens, W and Merletti, F and Richiardi, L and Talamini, R and Barzan, L and Kjaerheim, K and Macfarlane, GJ and Macfarlane, TV and Simonato, L and Canova, C and Agudo, A and Castellsagué, X and Lowry, R and Conway, DI and McKinney, PA and Healy, CM and Toner, ME and Znaor, A and Curado, MP and Koifman, S and Menezes, A and Wünsch-Filho, V and Neto, JE and Garrote, LF and Boccia, S and Cadoni, G and Arzani, D and Olshan, AF and Weissler, MC and Funkhouser, WK and Luo, J and Lubiński, J and Trubicka, J and Lener, M and Oszutowska, D and Schwartz, SM and Chen, C and Fish, S and Doody, DR and Muscat, JE and Lazarus, P and Gallagher, CJ and Chang, SC and Zhang, ZF and Wei, Q and Sturgis, EM and Wang, LE and Franceschi, S and Herrero, R and Kelsey, KT and McClean, MD and Marsit, CJ and Nelson, HH and Romkes, M and Buch, S and Nukui, T and Zhong, S and Lacko, M and Manni, JJ and Peters, WHM and Hung, RJ and McLaughlin, J and Vatten, L and Njølstad, I and Goodman, GE and Field, JK and Liloglou, T and Vineis, P and Clavel-Chapelon, F and Palli, D and Tumino, R and Krogh, V and Panico, S and González, CA and Quirós, JR and Martínez, C and Navarro, C and Ardanaz, E and Larrañaga, N (2011) A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genetics, 7 (3). ISSN 1553-7390

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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. © 2011 McKay et al.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
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
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHorwitz, Marshall S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2011
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 7
Number: 3
DOI or Unique Handle: 10.1371/journal.pgen.1001333
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Adult; Aged; Aldehyde Dehydrogenase--genetics; Continental Population Groups; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Head and Neck Neoplasms--enzymology; Head and Neck Neoplasms--epidemiology; Head and Neck Neoplasms--genetics; Humans; Male; Middle Aged; Risk Factors; Tumor Markers, Biological--genetics
Other ID: NLM PMC3060072
PubMed Central ID: PMC3060072
PubMed ID: 21437268
Date Deposited: 30 Aug 2012 14:32
Last Modified: 20 Jul 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/13813

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