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

Stefania Boccia, Gabriella Cadoni, Pagona Lagiou, Paolo Boffetta, Corina Lesseur, Brenda Diergaarde, Andrew F. Olshan, Victor Wünsch-Filho, Andrew R. Ness, Geoffrey Liu, Martin Lacko, José Eluf-Neto, Silvia Franceschi, Gary J. Macfarlane, Lorenzo Richiardi, Jerry Polesel, Kristina Kjaerheim, David Zaridze, Mattias Johansson, Ana M. MenezesMaria Paula Curado, Max Robinson, Wolfgang 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, H. Bas Bueno-De-Mesquita, Annika Steffen, Antonio Agudo, Oxana Shangina, Xiangjun Xiao, Valérie Gaborieau, Amélie Chabrier, Devasena Anantharaman, Christopher I. Amos, James D. Mckay, Paul Brennan

Risultato della ricerca: Contributo in rivistaArticolo in rivista

71 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1544-1550
Numero di pagine7
RivistaNature Genetics
Volume48
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Aged
  • Case-Control Studies
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genetics
  • Genome-Wide Association Study
  • HLA Antigens
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Mouth
  • Mouth Neoplasms
  • Papillomaviridae
  • Papillomavirus Infections
  • Pharyngeal Neoplasms

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