Epidemiologic and scientific research indicates that diet and other lifestyle factors have a significant influence on the risk of developing colon cancer. However, the influence of diet, physical activity, obesity, and other lifestyle factors on the outcome of patients with established colon cancer is virtually unknown. Randomized clinical trials demonstrate a significant survival advantage for individuals with stage III colon cancer who receive adjuvant fluorouracil-based chemotherapy. Nonetheless, 40-45% of stage III patients receiving current adjuvant chemotherapy will develop metastases. Patients often seek to understand what, if any, diet and lifestyle will reduce their chances of cancer recurrence as well as the potential toxicities associated with adjuvant therapy. Moreover, how diet and lifestyle influence prognosis may depend, in part, on molecular characteristics of the tumor. In response to a NIH Program Announcement, PA-06-404, "Studies of Energy Balance and Cancer in Humans," we propose to address these gaps in knowledge by utilizing a large, completed National Cancer Institute-sponsored adjuvant chemotherapy trial (CALGB 89803) in stage III colon cancer which provides a) two longitudinal prospective, validated assessments of diet, medication, and lifestyle;b) paraffin-embedded tumor specimens to examine how dietary factors interact with specific molecular alterations;and c) comprehensive data on cancer recurrence, mortality, and chemotherapy-related toxicity. Since pathologic stage, performance status, post-operative therapy and follow-up were carefully defined in this trial, residual confounding by disease characteristics and use of adjuvant therapy should be minimized. This database will provide a unique opportunity to examine the influence of diet (Aim 1), energy balance (Aim 2), and aspirin and other medications (Aim 3) on the risk of colon cancer recurrence, mortality, and chemotherapy-related toxicity. Each specific aim in this proposal extends current knowledge in these areas. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, this database will permit us to ascertain the influence of numerous factors on colon cancer survival, improve our understanding of colon cancer biology, and potentially offer substantive dietary and lifestyle recommendations for patients and health care providers.