A case-control study to examine the independent and combined effects of arylamine acetylator status and N-oxidation status, cigarette smoking, and high meat consumption on subsequent risk of pancreatic cancer is proposed. The proposal is based on the hypothesis that aromatic amines (AAs) are carcinogenic for the human pancreas; a view supported by our laboratory evidence. All cases of adenocarcinoma of the exocrine pancreas (N = 630) who are: 1) age 20 or above, 2) newly diagnosed during a three and one- half year period in the seven-county metropolitan area of Minneapolis/St. Paul, and 3) confirmed with a histological or clinical diagnosis of cancer through either pathology report, hospital based-tumor registry, or medical records, will be eligible for this study. Because of the relatively short survival time and the high percentage of clinically diagnosed cases, we will contract for the services of existing data managers within hospitals to assist in the early identification of the cases through physicians, pathology reports, initial discharge, and tumor registries. Controls will be frequency matched to the cases by sex and age (in 5-year age groups) and randomly selected from the same seven-county area as the cases. Controls aged 20 to 64 will be chosen by random digit dialing, and controls aged 65 and above will be selected from Health Care Financing Administration records. In-person interviews will be conducted and blood samples drawn by trained interviewer/phlebotomists at a time and location of the study subject's choice. Detailed information will be ascertained for each subject including: 1) arylamine acetylator and N-oxidation status; 2) complete cigarette smoking history; 3) dietary intake; 4) medical and family history; 5) occupational history; 6) complete allergy history; and 7) basic demographic information. Participants will be phenotyped with respect to acetylator and N-oxidation status by the examination of levels of caffeine metabolites in a urine specimen collected after ingestion of a 100 mg caffeine tablet. Blood samples will be used for genotypic determination of acetylator status and will be stored for future analyses. Statistical analyses will address the a priori hypotheses that: 1) high exposure to arylamines of smoking and dietary origin, rapid acetylator, and rapid N-oxidation status are independently associated with an increased risk of pancreatic cancer. The association between rapid acetylator status and pancreatic cancer will also be evaluated among smokers and heavy meat consumers.
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