DESCRIPTION (provided by applicant): Colorectal cancer is the second leading cause of cancer deaths in the United States. According to the American Cancer Society, more than 130,000 Americans will be diagnosed with cancer of the colon or rectum this year. Fortunately researchers are making extraordinary progress in the development and/or identification of agents that may delay or prevent colorectal cancer. These include pharmaceuticals such as the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are effective at preventing polyp formation in familial adenomatous polyposis (FAP) patients having a genetic predisposition to cancer. Epidemiological evidence suggests that long-term NSAID use is associated with a decreased risk of colon cancer in non-familial colon cancer as well. However, NSAIDs can produce serious side effects, including gastrointestinal bleeding and even death. One strategy to minimize toxicity of NSAIDs is to use very low doses in combination with other agents having complementary modes of action. Tea prevents intestinal and/or colorectal cancer in a variety of animal models. A combination of tea plus the NSAID sulindac was recently shown to be highly effective at preventing the formation of tumors in Apc[min] mice. These mice have a mutation in Apc (same gene altered in FAP) and, like humans with FAP, are genetically predisposed to develop large numbers of intestinal adenomas at an early age. This suggests that a combination of tea plus sulindac may be of benefit in treating humans with FAP. However, the majority of human colon cancers are not hereditary; instead their cause is unknown, but may be due to interaction of environmental and genetic factors. The A33[delta-N-beta-cat] mouse is an innovative new animal model that may be particularly appropriate as a mimic for non-familial colorectal cancer. A33[delta-N-beta-cat] mice express an oncogenic form of beta-catenin in their intestines. The A33[delta-N-beta-cat] mice do not develop multiple intestinal tumors at an early age like Apc[min] mice, but are highly susceptible to chemically induced colon cancer. The proposed studies are the first chemoprevention studies to be conducted in A33[delta-N-beta-cat] mice. These studies will examine the combined benefits of tea plus low-dose sulindac as preventive agents towards colon cancer. This research will provide valuable information on how dietary factors and pharmaceuticals interact in the prevention of intestinal cancer, and may also expedite future cancer prevention research through further validation of the A33[delta-N-beta-cat] mouse model.