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 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

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 HM

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 HM

Trichopoulou, Antonia

Linseisen, Jakob

Boeing, Heiner

Hallmans, Göran

Overvad, Kim

Tjønneland, Anne

Kumle, Merethe

Riboli, Elio

Välk, Kristjan

Vooder, 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

Horwitz, Marshall S

2019-02-01T15:03:40Z

2019-02-01T15:03:40Z

2011-03-17

2019-02-01T15:03:38Z

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.

1553-7390

1553-7404

https://hdl.handle.net/10161/17965

eng

Public Library of Science (PLoS)

PLoS genetics

10.1371/journal.pgen.1001333

Humans

Head and Neck Neoplasms

Genetic Predisposition to Disease

Aldehyde Dehydrogenase

Risk Factors

Gene Frequency

Adult

Aged

Middle Aged

Continental Population Groups

Female

Male

Genetic Variation

Genome-Wide Association Study

Biomarkers, Tumor

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

Journal article

Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

e1001333

3

School of Medicine

Duke

Duke Cancer Institute

Institutes and Centers

Population Health Sciences

Basic Science Departments

Medicine, Medical Oncology

Medicine

Clinical Science Departments

Published

7