Περίληψη:
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC. © 2021, The Author(s).
Συγγραφείς:
Ferreiro-Iglesias, A.
McKay, J.D.
Brenner, N.
Virani, S.
Lesseur, C.
Gaborieau, V.
Ness, A.R.
Hung, R.J.
Liu, G.
Diergaarde, B.
Olshan, A.F.
Hayes, N.
Weissler, M.C.
Schroeder, L.
Bender, N.
Pawlita, M.
Thomas, S.
Pring, M.
Dudding, T.
Kanterewicz, B.
Ferris, R.
Thomas, S.
Brhane, Y.
Díez-Obrero, V.
Milojevic, M.
Smith-Byrne, K.
Mariosa, D.
Johansson, M.J.
Herrero, R.
Boccia, S.
Cadoni, G.
Lacko, M.
Holcátová, I.
Ahrens, W.
Lagiou, P.
Lagiou, A.
Polesel, J.
Simonato, L.
Merletti, F.
Healy, C.M.
Hansen, B.T.
Nygård, M.
Conway, D.I.
Wright, S.
Macfarlane, T.V.
Robinson, M.
Alemany, L.
Agudo, A.
Znaor, A.
Amos, C.I.
Waterboer, T.
Brennan, P.
Λέξεις-κλειδιά:
capsid protein L1; HLA DQA1 antigen; HLA DQB1 antigen; HLA DRB1 antigen; protein antibody; protein E6; capsid protein; E6 protein, Human papillomavirus type 16; HLA antigen; oncoprotein; repressor protein; virus antibody, antibody; cancer; immune response; protein, adult; aged; antibody blood level; Article; cancer risk; controlled study; female; gene locus; genetic predisposition; genetic susceptibility; haplotype; HLA system; human; Human papillomavirus type 16; humoral immunity; innate immunity; major clinical study; male; middle aged; mouth cancer; nonhuman; oropharynx cancer; papillomavirus infection; serology; biosynthesis; case control study; classification; gene expression; genetics; genome-wide association study; Human papillomavirus type 16; immunology; meta analysis (topic); mouth tumor; oropharynx tumor; papillomavirus infection; pathogenicity; pathology; pathophysiology; quantitative trait locus; risk factor; smoking; virology, Human papillomavirus, Aged; Antibodies, Viral; Capsid Proteins; Case-Control Studies; Female; Gene Expression; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; HLA Antigens; Human papillomavirus 16; Humans; Immunity, Humoral; Male; Meta-Analysis as Topic; Middle Aged; Mouth Neoplasms; Oncogene Proteins, Viral; Oropharyngeal Neoplasms; Papillomavirus Infections; Quantitative Trait Loci; Repressor Proteins; Risk Factors; Smoking
