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

项目摘要 食道鳞状细胞癌(ESCC)是与癌症相关的死亡的第二大原因 东非的雄性。在乌干达西南部，ESCC的患病率正在上升，而 诊断率正在下降。此外，食管鳞癌仍因表现迟缓和生存不良而变得复杂。 尽管接受了治疗，但利率仍然很高。这些发病率和发病年龄的变化不能用已知的ESCC风险来解释 人乳头瘤病毒、酒精和烟草使用等因素作为这些危险因素的流行率 保持低位，保持不变。导致增长的额外的、潜在的可修改的风险因素 在ESCC中的作用尚未阐明。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ESCC风险增加的潜在解释。 目前的K43申请寻求建立在以前证明男性性别的横截面工作的基础上， 吸烟和饮酒是ESCC的危险因素。首先，这个奖项将提供一个机会来加强我的 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、胃肠病学和营养学方面的顶尖专家一起完成成功的学徒生涯。 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。 科学和技术。其次，我的ESCC患者队列将使前瞻性检查成为可能 多环芳烃暴露与ESCC的关系。我还将探索遗传和 该人群中食管鳞癌的分子特征。 拟议的职业发展活动和一系列研究将加深我们对 生物质燃料和饮食影响ESCC风险的生物学机制，主要关注DNA 甲基化作为一种媒介。这些发现可以提供对ESCC途径的新理解，这些途径可能导致 以创新方式鼓励对生活在ESCC高负担中的个人进行多因素风险因素修改 在撒哈拉以南非洲地区，这是一个难以实现的公共卫生目标。

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.