Integrated Epidemiologic Study of Ultra-processed Foods and Colorectal Cancer Survival

超加工食品与结直肠癌生存的综合流行病学研究

• 批准号: 10815098
• 负责人: Mengxi Du
• 金额: $ 9.13万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10815098
• 关键词: Acceleration; Adult; American; Biological; Biological Markers; Calories; Cancer Control; Cancer Etiology; Cancer Survivor; Cancer Survivorship; Carcinogens; Caring; Cessation of life; Cohort Studies; Colorectal Cancer; Consumption; Counseling; DNA Damage; Data; Diagnostic; Diet; Dietary Component; Dietary Intervention; Dietary intake; Disease; Eating; Etiology; Follow-Up Studies; Food; Food Processing; Gene Mutation; Genomics; Goals; Health Professional; Inflammatory Response; Intake; Intervention; Link; Long Term Survivorship; Malignant Neoplasms; Measures; Mentorship; Modeling; Molecular; Mutation; Nurses' Health Study; Nutrition Policy; Nutritional Science; Obesity; Oncology; Participant; Pathway interactions; Patients; Phase; Plasma; Postdoctoral Fellow; Process; Processed Meats; Prognosis; Prospective, cohort study; Public Health Schools; Recommendation; Relative Risks; Research; Research Project Grants; Research Training; Risk Assessment; Risk Estimate; Risk Factors; Role; Sampling; Schools; Somatic Mutation; Testing; Translating; Tumor Markers; Tumor Tissue; Woman; attributable mortality; biomarker identification; cancer diagnosis; cancer statistics; cancer survival; cancer therapy; career; career development; circulating biomarkers; clinical practice; cohort; colon cancer patients; colorectal cancer progression; colorectal cancer risk; comparative; design; dietary; epidemiologic data; epidemiology study; exome sequencing; food consumption; improved; innovation; insight; men; metabolomics; mortality; negative affect; novel; novel marker; nutrition; precision nutrition; precision oncology; risk stratification; skill acquisition; survival outcome; trend; tumor; tumor microenvironment; tumor progression

PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) remains a leading cause of cancer deaths in the US and is one of the cancers most strongly associated with a suboptimal diet. Within various dietary components, ultra-processed foods (UPFs) are emerging as an increasingly important risk factor for CRC. UPFs make up nearly 60% of Americans’ daily calories. A high UPF intake may increase CRC risk or worsen its prognosis through altered metabolites that may impact glycemic or inflammatory responses, or tumor microenvironment, resulting in cancer progression. Food processing may also introduce carcinogens and certain UPF components can contribute to somatic mutations. Besides, a high UPF intake is associated with excess intake of calories, leading to adiposity, an established risk factor for CRC. Thus, UPFs could be an important dietary risk factor for CRC progression and yet the UPF-CRC survival has not been adequately studied. While evidence suggests that CRC progression is associated with metabolites modulated by diet, the metabolomic profiles associated with UPFs remain to be characterized. Constituents of UPFs such as red or processed meats have been related to alkylating DNA damage and increased CRC mortality, yet the role of UPFs remains unclear. These unknowns highlight the critical need to comprehend the association between UPFs and CRC survival and the molecular determinants of this relationship for improving long-term CRC survivorship. Well-established large prospective cohort studies are crucial to offering rigorous data to elucidate the diet-disease association and infer causality. Advances in high-throughput metabolomic profiling and whole-exome sequencing (WES) show great promise to identify sensitive biomarkers that could better predict the diet-disease relationships. The overarching research goal of this F99/K00 proposal is to investigate the role of UPFs in CRC survival by integrating high throughput -omics and detailed dietary data collected among men and women from large cohorts. The F99 phase will focus on investigating the association between UPF intake and deaths due to CRC and all causes among CRC survivors (Aim 1); the K00 phase will shift the focus to investigating the molecular correlates of UPF-CRC survival relationship by integrating metabolomics profiling and tumor WES data and exploring the feasibility of a pilot intervention to reduce UPF intake among CRC patients (Aim 2). The research findings will inform dietary recommendations for CRC survivors, accelerate the discovery of novel biomarkers to pave the way for precision nutrition in oncology care, and provide new insights into nutrition interventions for improving the long-term survivorship of CRC. Under the mentorship of sponsors at Tufts Friedman School of Nutrition Science and Policy and Harvard T.H. Chan School of Public Health, the candidate will acquire rigorous research training and professional and career development skills for transition to an independent research career focus on studying the role of nutrition in cancer control and translate evidence into effective nutrition interventions and clinical practices to improve cancer survivorship.

项目概要/摘要 结直肠癌 (CRC) 仍然是美国癌症死亡的主要原因，也是最常见的癌症之一 与次优饮食密切相关。在各种膳食成分中，超加工食品 (UPF) 正成为 CRC 日益重要的危险因素。 UPF 占美国人日常生活的近 60% 卡路里。高 UPF 摄入量可能会增加 CRC 风险或因代谢改变而恶化其预后。 影响血糖或炎症反应或肿瘤微环境，导致癌症进展。食物 加工过程还可能引入致癌物质，某些 UPF 成分可能导致体细胞突变。 此外，高 UPF 摄入量会导致卡路里摄入过量，从而导致肥胖，这是一种既定风险 CRC 的因素。因此，UPF 可能是 CRC 进展的重要饮食危险因素，但 UPF-CRC 生存尚未得到充分研究。虽然有证据表明 CRC 进展与 虽然代谢物受饮食调节，但与 UPF 相关的代谢组学特征仍有待表征。 UPF 的成分（例如红肉或加工肉类）与烷基化 DNA 损伤和 CRC 死亡率增加，但 UPF 的作用仍不清楚。这些未知因素凸显了迫切需要 理解 UPF 与 CRC 生存之间的关联以及这种关系的分子决定因素 提高 CRC 的长期存活率。完善的大型前瞻性队列研究对于 提供严格的数据来阐明饮食与疾病的关联并推断因果关系。高通量方面的进展 代谢组学分析和全外显子组测序 (WES) 在识别敏感生物标志物方面显示出巨大的前景 这可以更好地预测饮食与疾病的关系。 F99/K00 提案的总体研究目标 旨在通过整合高通量组学和详细的饮食数据来研究 UPF 在 CRC 存活中的作用 从大群的男性和女性中收集。 F99阶段将重点调查关联 UPF 摄入量与 CRC 和 CRC 幸存者中所有原因导致的死亡之间的关系（目标 1）； K00阶段将 通过整合将重点转移到研究 UPF-CRC 生存关系的分子相关性 代谢组学分析和肿瘤 WES 数据，并探索试点干预措施降低 UPF 的可行性 CRC 患者的摄入量（目标 2）。研究结果将为结直肠癌的饮食建议提供参考 幸存者，加速发现新型生物标志物，为肿瘤护理中的精准营养铺平道路， 并为改善结直肠癌长期生存的营养干预措施提供新见解。下 塔夫茨弗里德曼营养科学与政策学院和哈佛大学 T.H. 赞助商的指导禅宗 公共卫生部门，候选人将获得严格的研究培训以及专业和职业发展 过渡到独立研究职业的技能重点是研究营养在癌症控制和中的作用 将证据转化为有效的营养干预措施和临床实践，以提高癌症生存率。