Air pollution and health disparities in liver disease and cancer

项目总结/摘要 K 01候选人Trang VoPham博士的长期目标是成为该领域的独立研究者。 使用地理空间科学和健康方法研究肝病环境危险因素的流行病学 差距。VoPham博士是一位技能高超的流行病学家和地理空间科学家，需要接受额外的培训 在（1）肝病流行病学，（2）健康差异，和（3）电子健康记录（EHR）分析她 成为一名成功的肝病独立研究者。她与导师们密切合作， 由肝病学、差异、流行病学和生物统计学领域的杰出研究者组成：乔治博士 Ioannou（初级导师）和共同导师Jason门多萨、Joel考夫曼和Kristin Berry博士，开发一种 全面的培训和研究计划，建立在她的肝癌研究经验， 流行病学和地理信息系统（GIS）。非酒精性脂肪肝（NAFLD）， 慢性肝病的常见原因，以及肝细胞癌（HCC），最常见的原发性肝癌类型， 肝癌在世界范围内的发病率正在增加。最近的证据，包括我们的初步数据，表明， 环境暴露于直径小于2.5微米的颗粒物（PM2.5），一种普遍存在的空气污染物， 增加NAFLD和HCC风险。此外，有证据表明，PM2.5可能对NAFLD产生不同的影响。 以及根据种族/民族、地理和性别的特定亚组中的HCC风险。然而，到目前为止， 研究是横断面的，仅限于暴露变异性很小的小研究区域，和/或没有 调整潜在混杂因素。电子病历是一种宝贵的和未充分利用的资源， 时变环境暴露的流行病学研究，包括丰富的居住地址信息 地点、临床状况和人口统计学。VoPham博士建议填补这些知识空白， 检查环境PM2.5暴露与NAFLD风险（目标1）和HCC风险（目标2）之间的关联， 确定PM2.5对NAFLD和HCC发病率差异的作用（按种族/民族、地理和性别） (Aim 3）。申请人将利用地理广阔，种族和民族多样化的退伍军人事务部 (VA)患者人群，通过将VA患者 使用地理信息系统，通过高分辨率、经验证的PM2.5暴露模型，从电子健康记录中对居住地址进行地理编码。 这项跨学科的研究将为PM2.5作为一种新的、可改变的、 NAFLD和HCC的生物学上合理的风险因素，以及作为驱动发病率的潜在环境因素 差异，提供翻译见解，以帮助识别肝病高风险个体。世界- 导师团队的跨学科专业知识，沿着优秀的支持性研究 弗雷德哈钦森癌症研究中心，华盛顿大学和弗吉尼亚州普吉特湾的环境 医疗保健系统，将确保博士VoPham实现她的所有职业发展和研究目标 并将促进她成为一名成功的肝病独立研究人员。

PROJECT SUMMARY / ABSTRACT The long-term goal of the K01 candidate, Dr. Trang VoPham, is to become an independent investigator in the epidemiology of environmental risk factors for liver disease using methods in geospatial science and health disparities. Dr. VoPham is a highly skilled epidemiologist and geospatial scientist and requires additional training in (1) liver disease epidemiology, (2) health disparities, and (3) electronic health record (EHR) analytics for her to become a successful independent researcher in liver disease. She has worked closely with her Mentors comprised of preeminent investigators in hepatology, disparities, epidemiology, and biostatistics: Dr. George Ioannou (Primary Mentor) and Co-Mentors, Drs. Jason Mendoza, Joel Kaufman, and Kristin Berry, to develop a comprehensive training and research program that builds on her research experience in liver cancer, epidemiology, and geographic information systems (GIS). Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, and hepatocellular carcinoma (HCC), the most common type of primary liver cancer, are increasing in incidence worldwide. Recent evidence, including our preliminary data, show that ambient exposure to particulate matter less than 2.5 microns in diameter (PM2.5), a ubiquitous air pollutant, may increase NAFLD and HCC risk. Further, there is evidence suggesting that PM2.5 may differentially impact NAFLD and HCC risk in particular subgroups according to race/ethnicity, geography, and sex. Yet, to date, epidemiologic studies have been cross-sectional, limited to small study areas with little exposure variability, and/or did not adjust for potential confounders. EHRs are a valuable and underutilized resource for large-scale, prospective epidemiologic studies of time-varying environmental exposures, including rich information on residential address locations, clinical conditions, and demographics. Dr. VoPham proposes to fill these gaps in knowledge by examining the associations between ambient PM2.5 exposure and NAFLD risk (Aim 1) and HCC risk (Aim 2) and determining the role of PM2.5 on NAFLD and HCC incidence disparities by race/ethnicity, geography, and sex (Aim 3). The applicant will leverage the geographically expansive, racially and ethnically diverse Veterans Affairs (VA) patient population, conducting a state-of-the-science geospatial exposure assessment by linking VA patient geocoded residential addresses from EHRs with a high-resolution, validated PM2.5 exposure model using GIS. This interdisciplinary research will provide new insights into the potential role of PM2.5 as a novel, modifiable, biologically plausible risk factor for NAFLD and HCC, and as a potential environmental factor driving incidence disparities, providing translational insights to help identify individuals at high risk for liver disease. The world- class interdisciplinary expertise of the Mentoring Team, along with the outstanding supportive research environment at Fred Hutchinson Cancer Research Center, University of Washington, and VA Puget Sound Health Care System, will ensure that Dr. VoPham achieves all of her career development and research goals and will facilitate her transition to become a successful independent researcher in liver disease.