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-Dąbrowska, 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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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.

Original languageEnglish
Pages (from-to)1544-1550
Number of pages7
JournalNature Genetics
Volume48
Issue number12
Early online dateOct 2016
DOIs
Publication statusPublished - Dec 2016

Keywords

  • epidemiology
  • genetics research
  • genome-wide association studies
  • oral cancer

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  • Cite this

    Lesseur, C., Diergaarde, B., Olshan, A. F., Wünsch-Filho, V., Ness, A. R., Liu, G., Lacko, M., Eluf-Neto, J., Franceschi, S., Lagiou, P., Macfarlane, G. J., Richiardi, L., Boccia, S., Polesel, J., Kjaerheim, K., Zaridze, D., Johansson, M., Menezes, A. M., Curado, M. P., ... Brennan, P. (2016). Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nature Genetics, 48(12), 1544-1550. https://doi.org/10.1038/ng.3685