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

项目摘要 食管鳞状细胞癌（ESCC）是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，而平均年龄为 诊断率下降。此外，食管鳞癌仍然是复杂的晚期表现和生存率低 尽管治疗。这些患病率和发病年龄的变化不能用已知的ESCC风险来解释 包括人乳头瘤病毒、酒精和烟草使用等因素作为这些危险因素的患病率 仍然很低，没有变化。其他潜在的可改变的风险因素导致了 在ESCC中的作用还有待阐明。生物质燃料中的多环芳烃暴露和/或 饮食来源是撒哈拉以南非洲ESCC风险增加的可能解释。 目前的K43应用程序试图建立在以前的横截面工作，证明男性性别， 吸烟和饮酒是ESCC的危险因素。首先，该奖项将提供机会，以加强我的 了解营养数据、癌症和遗传流行病学的测量和分析， 与癌症基因组学、胃肠病学和营养学领域的顶尖专家一起完成成功的实习。 拟议的培训将包括由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患者队列将使前瞻性检查， 多环芳烃暴露与食管鳞癌的关系。我还将探索基因和 ESCC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 甲基化作为媒介。这些发现可以为ESCC的途径提供新的理解， 创新方法，鼓励生活在ESCC高负担人群中的多因素风险因素调整 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.