Role of Vitamin D, Inflammation, and Energy Balance in Colorectal Cancer Survival

维生素 D、炎症和能量平衡在结直肠癌生存中的作用

• 批准号: 8304206
• 负责人: Kimmie Ng
• 金额: $ 17.78万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-19 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304206
• 关键词: Address; American Cancer Society; Archives; Attenuated; Biochemical Genetics; Biological; Biometry; Blood; C-Peptide; C-reactive protein; Calcifediol; Cancer Center; Cancer Control; Cancer Etiology; Cancer Patient; Cancer Prognosis; Cancer Survivor; Cancer and Leukemia Group B; Cells; Cessation of life; Characteristics; Chronic; Clinical; Collaborations; Colorectal Cancer; Consensus; DNA; Data; Diagnosis; Diet; Dietary Factors; Disease; Environment; Epidemiologic Studies; Epidemiology; Excision; Exercise; Exhibits; Funding Agency; Future; GC gene; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Goals; Health Professional; Inflammation; Inflammation Mediators; Inflammatory; Insulin; Insulin-Like Growth-Factor Binding Protein 1; Interleukin-6; Investigation; KRAS2 gene; Knowledge; Laboratories; Life Style; Link; Malignant Neoplasms; Measures; Mentorship; Mixed Function Oxygenases; Molecular; Molecular Genetics; Mutate; National Cancer Institute; Nurses' Health Study; Nutritional; Obesity; Outcome; PTGS2 gene; Paraffin Embedding; Pathogenesis; Pathway interactions; Patients; Peroxisome Proliferator-Activated Receptors; Physical activity; Plasma; Prognostic Factor; Public Health Schools; RXR; Research; Research Design; Research Personnel; Resources; Risk; Role; Somatomedins; Specimen; TNF gene; Training; United States; Variant; Vitamin D; Vitamin D3 Receptor; anticancer research; cancer recurrence; cancer therapy; chemotherapy; cohort; cyclooxygenase 2; dietary supplements; energy balance; experience; follow-up; human TNFRSF1A protein; improved; indexing; inflammatory marker; lifestyle factors; member; mortality; novel; nutrition; outcome forecast; overexpression; programs; prospective; skills; treatment strategy; tumor; tumor necrosis factor alpha receptor; tumor progression

DESCRIPTION (provided by applicant): Relatively little is known about the dietary and lifestyle factors that influence survival after a diagnosis of colorectal cancer. In fact, a consensus panel of the American Cancer Society recommended, "Properly conducted studies of the effect of nutrition and physical activity on the prognosis of cancer survivors are urgently needed, and should be a high priority for all academic and research funding agencies." Many of the nutritional and lifestyle factors that are thought to influence colorectal cancer progression (low vitamin D, high insulin, obesity, and physical inactivity) may operate through the vitamin D, inflammatory, and energy balance pathways in the cell. Elucidating the biological explanation for the link between these factors and colorectal cancer would enhance the acceptability of nutrition and exercise as critical for cancer treatment. To address this problem, the current proposal focuses on the investigation of biochemical, genetic, and dietary predictors of colorectal cancer recurrence and survival, with the ultimate goal of reducing mortality. Three inter-related pathways will be studied. For Aim 1, we will examine plasma levels of vitamin D, a vitamin D prediction score, and genetic variation within the pathway, and how these exposures interact with specific molecular alterations. For Aim 2, we will investigate plasma markers of inflammation and genetic variation in inflammation-related genes, in an effort to better understand the link between chronic inflammation and colorectal cancer. In addition, we will explore the interaction between these inflammatory markers and the vitamin D pathway. For Aim 3, we will examine a novel dietary index that estimates long-term systemic insulin exposure, as well as the relationship between members of the insulin-like growth factor pathway and vitamin D. A major strength of this proposal is the ability to examine these plasma, genetic, and dietary factors prospectively, using three large cohorts of colorectal cancer patients with repeated dietary and lifestyle assessments; archived blood, tumor, and DNA specimens; and comprehensive data on prognostic factors and cancer outcomes. By examining these aims, this project will improve the understanding of the mechanisms that underlie colorectal cancer pathogenesis and define practical treatment measures for this difficult disease. Moreover, the current proposal will allow the candidate to gain advanced skills in biostatistics and epidemiology, pursue a focused program in colorectal cancer research, and receive close, long-term mentorship from experienced and successful investigators, promoting her transition to an independent academic researcher. The intense collaboration and vast resources of the Dana-Farber/Harvard Cancer Center, Channing Laboratory, and Harvard School of Public Health provide an ideal environment for the candidate to receive the training and mentorship needed to become a leader in the field of cancer research.

描述(申请人提供)：对诊断为结直肠癌后影响存活率的饮食和生活方式因素知之甚少。事实上，美国癌症协会的一个共识小组建议：“关于营养和体力活动对癌症幸存者预后影响的适当研究是迫切需要的，应该是所有学术和研究资助机构的高度优先事项。”许多被认为影响结直肠癌进展的营养和生活方式因素(低维生素D、高胰岛素、肥胖和缺乏体力活动)可能通过细胞中的维生素D、炎症和能量平衡途径发挥作用。阐明这些因素与结直肠癌之间联系的生物学解释将提高营养和锻炼作为癌症治疗关键的可接受性。为了解决这一问题，目前的建议侧重于研究生化、遗传和饮食对结直肠癌复发和生存的预测因素，最终目标是降低死亡率。我们将研究三条相互关联的途径。对于目标1，我们将检查血浆维生素D水平、维生素D预测得分、途径中的遗传变异，以及这些暴露如何与特定的分子变化相互作用。对于目标2，我们将研究炎症的血浆标志物和炎症相关基因的遗传变异，以努力更好地了解慢性炎症与结直肠癌之间的联系。此外，我们还将探讨这些炎症标志物与维生素D途径之间的相互作用。对于目标3，我们将研究一种新的饮食指数，它可以评估长期全身胰岛素暴露，以及胰岛素样生长因子途径成员和维生素D之间的关系。这项建议的主要优点是能够前瞻性地检查这些血浆、遗传和饮食因素，使用三个重复进行饮食和生活方式评估的结直肠癌患者大队列；存档的血液、肿瘤和DNA样本；以及关于预后因素和癌症结果的综合数据。通过检查这些目标，该项目将提高对结直肠癌发病机制的理解，并确定这一疑难疾病的实际治疗措施。此外，目前的提案将允许候选人获得生物统计学和流行病学方面的高级技能，追求结直肠癌研究的重点项目，并从经验丰富和成功的研究人员那里获得密切的、长期的指导，促进她向独立学术研究人员的过渡。达纳-法伯/哈佛癌症中心、钱宁实验室和哈佛公共卫生学院的紧密合作和巨大资源为候选人提供了理想的环境，使其能够接受成为癌症研究领域领导者所需的培训和指导。