Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

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

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101 Scopus citations

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 × 10 â'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 × 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 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

Original languageEnglish
Pages (from-to)1544-1550
Number of pages7
JournalNature Genetics
Volume48
Issue number12
DOIs
StatePublished - 1 Dec 2016

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