Dietary and Lifestyle Determinants of Colon Cancer Recurrence and Survival

描述（由申请人提供）：流行病学和科学研究表明，饮食和其他生活方式因素对结肠癌的发病风险有重大影响。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，40-45%接受当前辅助化疗的III期患者将发生转移。患者经常试图了解哪些饮食和生活方式（如果有的话）会降低癌症复发的机会以及与辅助治疗相关的潜在毒性。此外，饮食和生活方式如何影响预后可能部分取决于肿瘤的分子特征。作为对美国国立卫生研究院项目公告PA-06-404“人类能量平衡与癌症研究”的回应，我们建议通过利用一项大型的、已完成的国家癌症研究所赞助的辅助化疗试验来填补这些知识空白（CALGB 89803），其提供a）饮食、药物和生活方式的两个纵向前瞻性、验证的评估; B）石蜡包埋的肿瘤标本，以检查饮食因素如何与特定的分子改变相互作用;和c）关于癌症复发、死亡率和化疗相关毒性的综合数据。由于在本试验中仔细定义了病理分期、体能状态、术后治疗和随访，因此应尽量减少疾病特征和辅助治疗使用的残留混杂。该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），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风险的影响。本提案中的每个具体目标都扩展了这些领域的现有知识。除了上述假设，这一组将允许快速检查未来的假设，因为他们出现。最终，这个数据库将使我们能够确定许多因素对结肠癌生存的影响，提高我们对结肠癌生物学的理解，并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.