Historically, Puerto Rico has experienced high rates of oral and pharynx cancers. The principle purpose of this study is to identify sociodemographic, behavioral, nutritional, dental, and occupational risk factors for oral and pharynx cancers in Puerto Rico. In addition, the study will evaluate the role of human papilloma virus, carcinogen- metabolizing alleles, and biomarkers for malignancy and malignant transformation using biological specimens from cases and controls. This study has a population-based case-control design with more than 500 cases ascertained from the cancer registry in Puerto Rico. The more than 600 control subjects are identified using two sampling frames providing good coverage and representation of the general population: a geographic area frame and Medicare rosters. Case and control subjects are interviewed in their homes using a standardized questionnaire which obtains data on a wide range of risk factors. Biological specimens are being obtained from selected study subjects. Specimens include a blood sample, a buccal cell scraping, a urine sample, and pathologic slides. With collaboration of several academic and commercial laboratories and experts, NIDR and NCI have been evaluating methods for collecting buccal scrapings and laboratory methods for evaluating the presence of human papillomavirus in buccal cell scrapings. Data will be analyzed to determine differences between cases and controls in the extent and distribution of potential behavioral risk factors, the presence and levels of viruses, molecular markers for malignancy and carcinogen-metabolizing alleles. This study will provide insights into the etiology of oral and pharyngeal cancer, and the reasons for the high incidence rates of these cancers in Puerto Rico. This year, laboratory analysis were begun to assess the following: human papilloma virus, p53, suppressor gene mutations, CYP1A1 gene (aryl hydrocarbon hydroxylase activity), GSTM1 (glutathione S-transferase-M1), GSTT1 (glutathione S-transferase theta 1), NAT1 (arylamine N- acetyltransferase-1), NAT2, NAT1 (arylamine N-acetyltransferase-2), AhR (aryl hydrocarbon receptor). Analyses estimating the risk associated with tobacco, alcohol, diet, oral and medical characteristics are nearing completion. Alcohol dehydrogenase type 3 genotype was determined in a subset of cases and controls. Analysis of the genotype and behavioral data jointly established that a higher rate of increase in the risk of oral and pharyngeal cancer per additional alcoholic drink per week was found among persons with the ADH type 3 genotype. This finding implicates ethanol's metabolite, acetaldehyde, in the etiology of oral and pharyngeal cancer. It suggests that both behavioral and genotypic characteristics need to be addressed in prevention efforts.