GENE-ENVIRONMENT EFFECTS AND COLON ADENOMAS

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DESCRIPTION: (Adapted from Applicant's Abstract). The long term goal of this application is to investigate effects of environmental exposures combined with heritable host factors on the risk for common cancers. The project will use epidemiology and molecular genetics and will focus on colon adenomas. Environmental exposures to be analyzed include: meat, cruciferous vegetables, and aspirin. High meat diets are believed to be risk factors, whereas cruciferous vegetables and aspirin are believed to be protective. Hereditary factors to be analyzed are variants of: N-acetyltransferases (NATs, which metabolize meat carcinogens); 4 different glutathione transferases (GSTs, which may clear anticarcinogens found in cruciferous vegetables), and the prostaglandin G/H synthetases (PGGS/PGHS) and cytosolic phospholipase A2 (cPLA2, variants of which may mimic the aspirin effect). A total of 9 different genes will be analyzed. The project will use subjects (1,000 cases and 1,000 controls) from an ongoing study titled, "A sigmoidoscopy-based case-control study of polyps." Subjects have been recruited from 2 sigmoidoscopy screening clinics at Kaiser Permanente Medical Centers in Los Angeles. Cases were asymptomatic with a first time diagnosis of at least 1 colorectal adenoma. Controls were selected from subjects free of adenomas. Data were collected from a self-administered dietary questionnaire, an in-person interview of non-dietary risk factors, a fasting blood sample, and pathology reports. The project will characterize polymorphic genes for NAT1, NAT2, GSTM1, GSTM3, GSTT1, PGHS-1, PGHS-2, and cPLA2 in all subjects. PCR assays, heteroduplex analysis, DNA sequencing, and gene expression assays will be used to molecularly characterize genes. Completion of the molecular analyses is intended to provide information on the mechanism of risk due to meat and the mechanisms of protection due to cruciferous vegetables and aspirin.