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.

项目摘要 食道鳞状细胞癌（ESCC）是癌症中与癌症相关死亡的第二大原因 东非的男性。在乌干达西南部，ESCC的患病率正在增加，而平均年龄 诊断正在减少。此外，ESCC仍然因迟到而生存不良而变得复杂 尽管有疗法的速度。这些变化的患病率和发病年龄无法通过已知的ESCC风险来解释 包括人类乳头瘤病毒，酒精和烟草作为这些危险因素的流行率在内的因素 保持较低和不变。其他有助于增加的，可能改变的风险因素 在ESCC中尚未阐明。多环芳烃在生物质燃料中暴露和/或 饮食来源是撒哈拉以南非洲地区ESCC风险增加的潜在解释。 当前的K43应用程序旨在基于以前证明男性的横断面工作， 吸烟和酒精作为ESCC的危险因素。首先，该奖项将为加强我的机会提供机会 了解营养数据，癌症和遗传流行病学的测量和分析，以及 与癌症基因组学，胃肠病学和营养领域的领先专家一起完成学徒制。 拟议的培训将包括通过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ESCC患者队列将实现前瞻性检查 多环芳族烃与ESCC的关系。我还将探索遗传和 ESCC在该人群中的分子特征。 拟议的职业发展活动和一系列研究将加深我们对 生物量燃料和饮食会影响ESCC风险的生物学机制，主要关注DNA 甲基化作为介体。这些发现可以为通往ESCC的途径提供新的了解，这可能会导致 以创新的方式鼓励居住在ESCC高负担中的个人的多因素风险因素修改 撒哈拉以南非洲的地区，这是一个难以实现的公共卫生目标。