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

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 ca...

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Hauptverfasser:	Lesseur, Corina, Diergaarde, Brenda, Olshan, Andrew F, Wünsch-Filho, Victor, Ness, Andrew R, Liu, Geoffrey, Lacko, Martin, Eluf-Neto, José, Franceschi, Silvia, Lagiou, Pagona, Macfarlane, Gary J, Richiardi, Lorenzo, Boccia, Stefania, Polesel, Jerry, Kjaerheim, Kristina, Zaridze, David, Johansson, Mattias, Menezes, Ana A, Curado, Maria Paula, Robinson, Max, Ahrens, Wolfgang, Canova, Crisitna, Znaor, Ariana, Castellsagué, Xavier, Conway, David I, Holcátová, Ivana, Mates, Dana, Vidensky, Marta, Healy, Claire M, Szeszenia-Dbrowska, Neonila, Fabianova, Eleonora, Lissowska, Jolanta, Grandis, Jennifer R, Weissler, Mark C, Tajara, Eloiza H, Nunes, Fabio D, Carvalho, Marcos B. de, 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, Valérie, Chabrier, Amélie, Anantharaman, Devasena, Boffetta, Paolo, Amos, Christopher I, McKay, James D, Brennan, Paul
Format:	Artikel
Sprache:	eng
Schlagworte:	Càncer de boca Oral cancer Papillomaviruses Papil·lomavirus
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Zusammenfassung:	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-DRB11301-HLA-DQA10103-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.