) The long-term goal is to study effects of environmental exposures combined with heritable host factor on the risks for common cancers. The project uses epidemiology and molecular genetic approaches and focuses on cruciferous vegetables (like broccoli) and colon polyps, which lead to cancer. Hereditary factors to be analyzed are variants of the enzymes that help the body get rid of cancer-causing chemicals. The enzymes are called glutathione transferase, glucuronosyltransferases, quinone reductases, and epoxide hydrolases. Special compounds in broccoli raise the levels of these enzymes in the body. However, some glutathione transferase also cause the body to excrete the special compounds. People have different forms of the enzymes, and the various forms may influence their risk for polyps. By studying the various forms of the enzymes in people with and without polyps, we may be able to figure out more precisely how broccoli protects people from cancer. We may also discover better ways to prevent cancer. The project will use subjects (1,000 cases and 1,000 controls) who are part of an ongoing study titled, """"""""A sigmoidoscopy-based case-control study of polyps.' Subjects have been recruited from two sigmoidoscopy screening clinics at Kaiser Permanente Medical Centers in Los Angeles. Cases were asymptomatic with a first-time diagnosis of at least one colorectal adenoma. Controls were selected from subjects who were free of polyps. 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, in all subjects, polymorphic genes for GSTM1, GSTM3, GSTT1, GSTP1, NQO1, EPHX1, UGTL *1, UGTL *6, and UGTL *02. Most of these genes have received no attention from epidemiologists, because large molecular studies have not been attempted. PCR assays, heteroduplex analysis, DNA sequencing, and gene expression assays will be used to molecularly characterize the genes. Completion of the molecular analyses will provide information on the mechanism of protection due to broccoli. Prevention of colon cancer could be improved.
