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.

• MeSH
• celogenomová asociační studie MeSH
• exprese genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• HLA antigeny klasifikace   genetika   imunologie   MeSH
• humorální imunita * MeSH
• infekce papilomavirem genetika   imunologie   patologie   virologie   MeSH
• kouření patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   patogenita   MeSH
• lokus kvantitativního znaku MeSH
• metaanalýza jako téma MeSH
• nádory orofaryngu genetika   imunologie   patologie   virologie   MeSH
• nádory úst genetika   imunologie   patologie   virologie   MeSH
• onkogenní proteiny virové genetika   imunologie   MeSH
• protilátky virové biosyntéza   MeSH
• represorové proteiny genetika   imunologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• virové plášťové proteiny genetika   imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• kouření škodlivé účinky   epidemiologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory hlavy a krku epidemiologie   etiologie   MeSH
• nádory hrtanu epidemiologie   etiologie   MeSH
• nádory orofaryngu epidemiologie   etiologie   MeSH
• nádory úst epidemiologie   etiologie   MeSH
• pití alkoholu škodlivé účinky   epidemiologie   patologie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

• MeSH
• dospělí MeSH
• kouření cigaret škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hlavy a krku etiologie   patologie   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH