Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.

Objective: To evaluate the association of oral health (OH), dental care (DC) and mouthwash with tumors of the upper-aerodigestive tract (UADT), and to which extend enzymes involved in the metabolism of alcohol modify the effect of alcohol-based mouthwashes.' Materials and Methods: Subjects were interviewed about OH and DC behaviors. Mouthwash use was analyzed in relation to alcohol dehydrogenase genes (ADH1B,ADH1C,ADH7) and one aldehyde dehydrogenase gene (ALDH2) known to be associated with head and neck cancers. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models. Results: ORs of low versus high scores of DC and OH were 2.36[CI=1. , respectively, for all UADT sites combined. The OR for use of mouthwash 3 or more times/day was 3.23[CI=1. 68-6.19]. The OR for the rare variant ADH7 coding for fast ethanol metabolism was lower in ) as compared to ) indicating effect modification (pheterogeneity=0.65) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2. Conclusions: Poor OH and DC are independent risk factors for UADT. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be clarified. Materials and MethodsSubjects were interviewed about OH and DC behaviors. Mouthwash use was analyzed in relation to alcohol dehydrogenase genes (ADH1B,ADH1C,ADH7) and one aldehyde dehydrogenase gene (ALDH2) known to be associated with head and neck cancers.Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models. Results ORs ConclusionsPoor OH and DC are independent risk factors for UADT. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be clarified. 5

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Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of falsepositive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend < 0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 À47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend = 0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend = 0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk ( for both, P trend = 0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways. [Cancer Res 2009;69(7):2956-65]