Genome-Wide Association Analyses Identify New Susceptibility Loci for Oral Cavity and Pharyngeal Cancer

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Citation

Lesseur, Corina; Diergaarde, Brenda; Olshan, Andrew F.; Wunsch-Filho, Victor; Ness, Andrew R.; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, Jose; Franceschi, Silvia; & Lagiou, Pagona, et al. (2016). Genome-Wide Association Analyses Identify New Susceptibility Loci for Oral Cavity and Pharyngeal Cancer. Nature Genetics, 48(12), 1544-1552. PMCID: PMC5131845

Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 x 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 x 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 x 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

URL

http://dx.doi.org/10.1038/ng.3685

Reference Type

Journal Article

Year Published

2016

Journal Title

Nature Genetics

Author(s)

Lesseur, Corina
Diergaarde, Brenda
Olshan, Andrew F.
Wunsch-Filho, Victor
Ness, Andrew R.
Liu, Geoffrey
Lacko, Martin
Eluf-Neto, Jose
Franceschi, Silvia
Lagiou, Pagona
Macfarlane, Gary J.
Richiardi, Lorenzo
Boccia, Stefania
Polesel, Jerry
Kjaerheim, Kristina
Zaridze, David
Johansson, Mattias
Menezes, Ana M.
Curado, Maria Paula
Robinson, Max
Ahrens, Wolfgang
Canova, Cristina
Znaor, Ariana
Castellsague, Xavier
Conway, David I.
Holcatova, Ivana
Mates, Dana
Vilensky, Marta
Healy, Claire M.
Szeszenia-Dabrowska, Neonila
Fabianova, Eleonora
Lissowska, Jolanta
Grandis, Jennifer R.
Weissler, Mark Christian
Tajara, Eloiza H.
Nunes, Fabio D.
de Carvalho, Marcos Brasilino
Thomas, Steve
Hung, Rayjean J.
Peters, Wilbert H. M.
Herrero, Rolando
Cadoni, Gabriella
Bueno-de-Mesquita, H. Bas
Steffen, Annika
Agudo, Antonio
Shangina, Oxana
Xiao, Xiangjun
Gaborieau, Valerie
Chabrier, Amelie
Anantharaman, Devasena
Boffetta, Paolo
Amos, Christopher I.
McKay, James D.
Brennan, Paul

PMCID

PMC5131845

ORCiD

Olshan - 0000-0001-9115-5128