We propose to expand our study of large bowel cancer by obtaining environmental and genetic data from individuals with rectal and rectosigmoid junction tumors. We will use the same methods developed and implemented in our original study of colon cancer (CA48998).
The aims of the study are to look at the independent and interactive associations between environmental and genetic factors as they relate to risk of developing rectal cancer. We propose to evaluate the independent and interactive effects of energy and energy providing nutrients, calcium, fiber, folic acid, carotenoids, and foods containing these nutrients on colorectal cancer risk. Additionally, we propose to evaluate rectal cancer risk from physical activity, tobacco, alcohol (and specific types of alcohol), body size, aspirin and/or nonsteroidal anti-inflammatory drugs, family history of colorectal cancer as independent risk factors and as they interact with dietary factors. We propose to look at the interaction between environmental factors and genetic factors, both those inherited (common polymorphisms of APC gene, acetylator status and glutathione-S-transferase null genotype (GSTM-1), and germline mutations of mismatch repair genes), and those which are acquired (p53, K-ras, and microsatellite instability). We also will evaluate the clinical implications of genetic alterations, both those inherited and acquired. Environmental data will be obtained from 1200 cases and 1200 population-based controls. Interviews will be conducted using computerized questionnaire developed for CA48998. Blood will be drawn by interviewers/phlebotomists at the time of the interview. Paraffin blocks will be abstracted from area hospitals as is currently being done for colon cancer cases. Genetic analyses will be conducted at the university of Utah. Data analysis will focus on independent and interactive effects of environmental factors; the interaction between inherited genetic factors and environmental exposures; and the impact of environmental factors on acquiring genetic mutations (using a case-case approach as well as a case-control approach). Using survival analysis, we will evaluate the impact of genetic characteristics of tumors on survival. A major strength of this study will be our ability to determine risk factors (both environmental and genetic factors) using the same research tools which we have done for color cancer, thus gaining a better understanding of the etiology of large bowel cancer.
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