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

• DOI: 10.1038/ng.3685
• Publication Date: 2016-10-17T16:04:17Z
• Authors: 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 Robinson; Wolfgang Ahrens; Cristina Canova; Ariana Znaor; Xavier Castellsagué; David I Conway; Ivana Holcátová; Dana Mates; Marta Vilensky; Claire M Healy; Neonila Szeszenia...; 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-Me...; Annika Steffen; Antonio Agudo; Oxana Shangina; Xiangjun Xiao; Valérie Gaborieau; Amélie Chabrier; Devasena Ananthar...; Paolo Boffetta; Christopher I Amos; James D McKay; Paul Brennan
• Keywords: Genome-wide Association Study

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 8 loci (P<5x10–8), 7 of which are novel 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 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 revealed a protective association with the class II haplotype DRB1*1301-DQA1*0103-DQB1*0603 (odds ratio (OR)=0.59, P=2.7x10–9). Stratified analyses on a subgroup of oropharyngeal cases with human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR=0.23, P=1.6x10–6) compared to HPV-negative cancers (OR=0.75, P=0.16).