Dietary and Lifestyle Determinants of Colon Cancer Recurrence and Survival

描述(申请人提供)：流行病学和科学研究表明，饮食和其他生活方式因素对患结肠癌的风险有重大影响。然而，饮食、体力活动、肥胖和其他生活方式因素对已确诊结肠癌患者预后的影响几乎是未知的。随机临床试验表明，接受以氟尿嘧啶为基础的辅助化疗的III期结肠癌患者具有显著的生存优势。尽管如此，接受当前辅助化疗的III期患者中有40%-45%将发生转移。患者经常试图了解，如果有的话，饮食和生活方式将降低他们癌症复发的机会，以及与辅助治疗相关的潜在毒性。此外，饮食和生活方式对预后的影响可能部分取决于肿瘤的分子特征。针对美国国立卫生研究院的一项计划公告PA-06-404，“能量平衡与人类癌症研究”，我们建议利用一项由美国国立癌症研究所赞助的针对III期结肠癌的大型、完整的辅助化疗试验(CALGB 89803)来解决这些知识空白，该试验提供：a)两项对饮食、药物和生活方式进行的前瞻性、有效性评估；b)石蜡包埋肿瘤标本，以检查饮食因素如何与特定分子变化相互作用；以及c)关于癌症复发、死亡率和化疗相关毒性的全面数据。由于本试验仔细定义了病理分期、表现状态、术后治疗和随访，应尽量减少因疾病特征和辅助治疗的使用而造成的残留混淆。这个数据库将提供一个独特的机会来检查饮食(目标1)、能量平衡(目标2)以及阿司匹林和其他药物(目标3)对结肠癌复发、死亡率和化疗相关毒性的影响。该提案中的每一项具体目标都扩展了这些领域的现有知识。除了上述假设之外，这一队列将允许在未来假设出现时对其进行快速检查。最终，这个数据库将使我们能够确定许多因素对结肠癌存活率的影响，提高我们对结肠癌生物学的理解，并有可能为患者和医疗保健提供者提供实质性的饮食和生活方式建议。

DESCRIPTION (provided by applicant): 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.