Polycyclic aromatic hydrocarbons exposure and dietary risk of Esophageal squamous cell carcinoma in Uganda

乌干达多环芳烃暴露和食管鳞状细胞癌的饮食风险

• 批准号: 9897608
• 负责人: Samson Okello
• 金额: $ 9.16万
• 依托单位: MBARARA UNIVERSITY/SCIENCE/ TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897608
• 关键词: Accounting; Affect; Africa; Africa South of the Sahara; Age; Age of Onset; Alcohol consumption; Alcohols; Area; Aromatic Polycyclic Hydrocarbons; Attention; Award; Behavioral; Biological; Cancer Etiology; Carcinogens; Case-Control Studies; Cessation of life; Charcoal; Country; DNA Methylation; Data; Diagnosis; Diet; Dietary Practices; Disease Progression; Eastern Africa; Educational process of instructing; Environmental Monitoring; Epidemiology; Epigenetic Process; Epithelial; Epithelium; Esophageal Squamous Cell Carcinoma; Esophageal Tissue; Esophagus; Exposure to; First Independent Research Support and Transition Awards; Food Processing; Gastroenterology; Gastrointestinal Endoscopy; Gender; Genomics; Geography; Goals; Histologic; Hospital Referrals; Human Papillomavirus; Individual; Internal Medicine; Intervention; Lead; Learning; Life; Malignant neoplasm of esophagus; Measurement; Measures; Mediator of activation protein; Medicine; Mentors; Methods; Milk; Modeling; Modification; Molecular Profiling; Morbidity - disease rate; Nutritional; Participant; Pathway interactions; Patients; Phenotype; Population; Population Attributable Risks; Prevalence; Prevention; Preventive Intervention; Public Health; Quality of life; Research Infrastructure; Risk; Risk Factors; Science; Series; Services; Smoking; Somatic Mutation; Source; Southern Africa; Surveys; Survival Rate; Teaching Hospitals; Techniques; Technology; Testing; Therapeutic Intervention; Tobacco use; Training; Uganda; Universities; Work; apprenticeship; arm; biomass fuel; cancer epidemiology; cancer genomics; carcinogenicity; career development; cohort; design; epigenomics; food consumption; food preparation; genetic epidemiology; genetic signature; genome-wide; health goals; high risk population; improved; innovation; lecturer; low and middle-income countries; male; modifiable risk; mortality; novel; nutrition; outcome forecast; prevent; prospective; rural area; sex; upper gastrointestinal cancer

Project Summary Esophageal squamous cell carcinoma (ESCC) is the second leading cause of cancer-related death among males in East Africa. In southwestern Uganda, the prevalence of ESCC is increasing while the mean age of diagnosis is decreasing. In addition, ESCC continues to be complicated by late presentation and poor survival rates despite therapy. These changing prevalence and age of onset cannot be explained by known ESCC risk factors including human papillomavirus, alcohol and tobacco use as the prevalence of these risk factors remains low and unchanged. Additional, potentially modifiable risk factors that are contributing to the increase in ESCC have yet to be elucidated. Polycyclic aromatic hydrocarbons exposures in biomass fuel and/or dietary sources are potential explanations of the heightened risk of ESCC in sub-Saharan Africa. The current K43 application seeks to build on previous cross-sectional work that demonstrates male sex, smoking and alcohol as risk factors for ESCC. First, the award will provide the opportunity to strengthen my understanding of measurement and analysis of nutritional data, cancer and genetic epidemiology, and to complete successful apprenticeships with leading experts in cancer genomics, gastroenterology, and nutrition. The proposed training will include brief courses offered through Harvard University and Mbarara University of Science and Technology. Second, my cohort of ESCC patients will enable prospective examination of relationships of polycyclic aromatic hydrocarbon exposures with ESCC. I will also explore genetic and molecular signatures of ESCC in this population. The proposed career development activities and series of studies will deepen our understanding of the biological mechanisms through which biomass fuel and diet affects ESCC risk, with a primary focus on DNA methylation as a mediator. These findings can provide new understanding of pathways to ESCC that may lead to innovative ways to encourage multifactorial risk factor modification in individuals living in ESCC high burden areas in sub-Saharan Africa, a public health goal that has been difficult to attain.

项目概要 食管鳞状细胞癌（ESCC）是癌症相关死亡的第二大原因 东非男性。在乌干达西南部，食管鳞癌的患病率正在增加，而平均年龄 诊断率正在下降。此外，食管鳞癌因晚期就诊和生存率低而变得复杂化 尽管接受治疗，但仍会发生率。这些变化的患病率和发病年龄不能用已知的食管鳞癌风险来解释 包括人乳头瘤病毒、饮酒和吸烟在内的这些风险因素的流行率 保持低位且不变。导致增加的其他潜在可改变的风险因素 ESCC 中的情况尚未阐明。生物质燃料和/或中的多环芳烃暴露 饮食来源是撒哈拉以南非洲地区食管鳞癌风险升高的潜在解释。 当前的 K43 应用程序旨在建立在先前展示男性性别的横断面工作的基础上， 吸烟和饮酒是 ESCC 的危险因素。首先，该奖项将提供加强我的机会 了解营养数据、癌症和遗传流行病学的测量和分析，并 与癌症基因组学、胃肠病学和营养学领域的领先专家一起成功完成学徒期。 拟议的培训将包括哈佛大学和姆巴拉拉大学提供的简短课程 科学技术。其次，我的食管鳞癌患者队列将能够进行前瞻性检查 多环芳烃暴露与 ESCC 的关系。我还将探索遗传和 该人群中 ESCC 的分子特征。 拟议的职业发展活动和系列研究将加深我们对 生物质燃料和饮食影响 ESCC 风险的生物机制，主要关注 DNA 甲基化作为介质。这些发现可以为食管鳞癌的途径提供新的认识，从而可能导致 鼓励 ESCC 高负担个体改变多因素危险因素的创新方法 在撒哈拉以南非洲地区，这一公共卫生目标一直难以实现。