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

  • Author(s): 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 M;
  • Curado, Maria Paula;
  • Robinson, Max;
  • Ahrens, Wolfgang;
  • Canova, Cristina;
  • Znaor, Ariana;
  • Castellsagué, Xavier;
  • Conway, David I;
  • Holcátová, Ivana;
  • Mates, Dana;
  • Vilensky, Marta;
  • Healy, Claire M;
  • Healy, Claire M;
  • Szeszenia-Dąbrowska, Neonila;
  • Fabiánová, Eleonóra;
  • Lissowska, Jolanta;
  • Grandis, Jennifer R;
  • Weissler, Mark C;
  • Tajara, Eloiza H;
  • Nunes, Fabio D;
  • de Carvalho, Marcos B;
  • Thomas, Steve;
  • Hung, Rayjean J;
  • Peters, Wilbert HM;
  • 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
  • et al.

Published Web Location

https://doi.org/10.1038/ng.3685
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 × 10-8), 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.

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