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 à 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-DRB1â 1301-HLA-DQA1â 0103-HLA-DQB1â 0603 (odds ratio (OR) = 0.59, P = 2.7 à 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 à 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
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., Robinson, M., Ahrens, W., Canova, C., Znaor, A., Castellsagué, X., Conway, D. I., Holcátová, I., Mates, D., Vilensky, M., Healy, C. M., Szeszenia-Dabrowska, N., Fabiánová, E., Lissowska, J., Grandis, J. R., Weissler, M. C., Tajara, E. H., Nunes, F. D., De Carvalho, M. B., Thomas, S., Hung, R. J., Peters, W. H. M., Herrero, R., Cadoni, G., Bueno-De-Mesquita, H. B., Steffen, A., Agudo, A., Shangina, O., Xiao, X., Gaborieau, V., Chabrier, A., Anantharaman, D., Boffetta, P., Amos, C. I., Mckay, J. D., Brennan, P., Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer, <<NATURE GENETICS>>, 2016; 48 (12): 1544-1550. [doi:10.1038/ng.3685] [https://hdl.handle.net/10807/125409]
Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer
Lagiou, Pagona;Boccia, Stefania;Cadoni, Gabriella;Boffetta, Paolo;
2016
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 à 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-DRB1â 1301-HLA-DQA1â 0103-HLA-DQB1â 0603 (odds ratio (OR) = 0.59, P = 2.7 à 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 à 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
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