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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.
Author(s): Lesseur C, Diergaarde B, Olshan AF, Wunsch V, Ness AR, Liu G, Lacko M, Eluf-Neto J, Franceschi S, Lagiou P, Macfarlane GJ, Richiardi L, Boccia S, Polesel J, Kjaerheim K, Zaridze D, Johanson M, Menezes AM, Curado MP, Robinson M, Ahrens W, Canova C, Znaor A, Castellsague X, Conway DI, Holcatova I, Mates D, Vidensky M, Healy CM, Szeszenia-Dbrowska N, Fabianova E, Lissowska J, Grandis JR, Weissler MC, Tajara EH, Nunes FD, de Carvalho MB, Thomas S, Hung RJ, Peters WHM, Herrero R, Cadoni G, Bueno-De-Mesquita HB, Steffen A, Agudo A, Shangina O, Xiao XJ, Gaborieau V, Chabrier A, Anantharaman D, Boffetta P, Amos CI, Mckay JD, Brennan P
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2016
Volume: 48
Issue: 12
Pages: 1544-1550
Print publication date: 01/12/2016
Online publication date: 17/10/2016
Acceptance date: 01/09/2016
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/ng.3685
DOI: 10.1038/ng.3685
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