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 × 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.

In:Nature Genetics: Springer Science and Business Media LLC48:12, s. 1544-15501061-40361546-1718

By the author/editor: Lesseur, Corina; Diergaarde, Bren ...; Olshan, Andrew F; Wünsch-Filho, Vi ...; Ness, Andrew R; Liu, Geoffrey; show more...; Lacko, Martin; Eluf-Neto, José; Franceschi, Silv ...; Lagiou, Pagona; Macfarlane, Gary ...; Richiardi, Loren ...; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Krist ...; Zaridze, David; Johansson, Matti ...; Menezes, Ana M; Curado, Maria Pa ...; Robinson, Max; Ahrens, Wolfgang; Canova, Cristina; Znaor, Ariana; Castellsagué, Xa ...; Conway, David I; Holcátová, Ivana; Mates, Dana; Vilensky, Marta; Healy, Claire M; Szeszenia-Dąbrow ...; Fabiánová, Eleon ...; Lissowska, Jolan ...; Grandis, Jennife ...; Weissler, Mark C; Tajara, Eloiza H; Nunes, Fabio D; de Carvalho, Mar ...; Thomas, Steve; Hung, Rayjean J; Peters, Wilbert ...; Herrero, Rolando; Cadoni, Gabriell ...; Bueno-de-Mesquit ...; Steffen, Annika; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valér ...; Chabrier, Amélie; Anantharaman, De ...; Boffetta, Paolo; Amos, Christophe ...; McKay, James D; Brennan, Paul; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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