Elucidating Lung Cancer Etiology Among Asian American Female Never Smokers

阐明从不吸烟的亚裔美国女性肺癌病因

基本信息

批准号：
10527364
负责人：
Moon Shao-Chuang Chen
金额：
$ 65.07万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10527364
关键词：
Adenocarcinoma Affect Age Air Pollutants Asia Asian Asian Americans Attention Body Size California Cancer Etiology Case/Control Studies Cessation of life Chinese Communicable Diseases Data Data Set Diagnosis Disease Disparity East Asian Environmental Epidemiology Epidermal Growth Factor Receptor Ethnic Origin Ethnic Population Etiology Exposure to Female Frequencies Genetic Histology Hormone use Incidence Individual Intervention Japanese Joints Koreans Low Prevalence Malignant Neoplasms Malignant neoplasm of lung Medical Oncology Methods Molecular Epidemiology Mutation Normal tissue morphology Not Hispanic or Latino Oils Pathway interactions Population Prevention strategy Reproductive History Research Risk Risk Factors Science Smoke Smoking Smoking History Social Environment Somatic Mutation Testing Tissue Sample United States Woman ambient air pollution burden of illness cancer epidemiology cancer health disparity cancer risk case control cohort community engaged research cooking design exome sequencing genomic data health inequalities hormone therapy improved indoor concentrations indoor pollutant neoplasm registry never smoker never smoking novel population based racial population smoking prevalence social epidemiology trend tumor

项目摘要

Abstract Lung cancer in never smokers (LCINS) is a disease and disparity that disproportionately affects Asian American (AA) females. In contrast to declining incidence trends seen among most racial/ethnic groups, incidence of lung cancer, especially adenocarcinoma, has been increasing in most AA ethnic groups. The majority of AA females, upwards of nearly 90% among Chinese, diagnosed with lung cancer have never smoked. There is very little known of the contributing risk factors to the high and increasing incidence rates of LCINS among AA females, particularly as risk factors identified in studies in Asia may have limited significance among AA populations. Moreover, there is limited understanding of the relationships between the mutational signatures of tumors among this population and their associated risk factors. Such information will improve our understanding of the underlying potential mechanistic pathways. Thus, the overall objective of this study is to identify the attributable risk of known, putative, and suspected risk factors for lung cancer among AA female never smokers. Recognizing that currently there are no U.S. datasets nor existing cohorts with data for evaluating putative and suspected risk factors that may be most relevant to this population, we propose a robust, population-based case-control study, leveraging early-case ascertainment methods from cancer registries and tested state-of-the-science approaches for unbiased control ascertainment. With high- quality, multilevel data collected from an estimated 600 female AA never-smoker lung cancer cases and 600 ethnicity and age frequency-matched controls, we aim to: Aim 1a. Identify risk factors for LCINS among AA females, with attention to differences by histology and EGFR (epidermal growth factor receptor) status (determined using whole exome sequencing [WES]), and focusing on multi-level factors including: a) genetic ancestry; b) individual- level exposures, including putative and suspected risk factors; and c) contextual-level risk factors including indoor and ambient air pollutants and the social environment, with consideration of nativity and years in the U.S. versus Asia; Aim 1b. Determine the independent and joint contributions of multi-level risk factors to LCINS among AA females by calculating the attributable risk for each risk factor, individually and in total; Aim 2a. Characterize the mutational landscape of LCINS among AA females, through WES of paired tumor-normal tissue samples to define somatic mutation profiles, mutational signatures, and EGFR status of LCINS AA females; and Aim 2b. Identify multi- level risk factors associated with the major mutational tumor features. All aims will assess potential differences by EGFR status. The proposed research will involve the assembly of the largest population-based lung cancer case- control dataset, with associated genetic and tumor genomic data, for never-smoking AA women. It will provide a first- ever opportunity to evaluate detailed multilevel factors contributing to the lung cancer disparity in distinct AA ethnic groups. A clear understanding of the etiologic factors underlying the high and increasing lung cancer risk among AA never-smoker females is necessary for designing the appropriate prevention strategies to reduce their high burden of disease.

抽象的从不吸烟者肺癌 (LCINS) 是一种对亚裔美国人 (AA) 影响尤为严重的疾病和差异女性。与大多数种族/族裔群体的发病率下降趋势相反，肺癌的发病率尤其是腺癌，在大多数 AA 族群中呈上升趋势。大多数 AA 女性，近90%的中国肺癌患者从未吸烟。对此人们知之甚少 AA 女性中 LCINS 发病率高且不断增加的危险因素，特别是作为风险因素亚洲研究中确定的因素在 AA 人群中的意义可能有限。此外，还有有限了解该人群中肿瘤突变特征及其之间的关系相关的风险因素。这些信息将提高我们对潜在机制的理解途径。因此，本研究的总体目标是确定已知、假定和可疑的可归因风险 AA 女性从不吸烟者患肺癌的危险因素。认识到目前没有美国数据集也没有现有的队列数据来评估可能与此最相关的假定和可疑的风险因素人群，我们提出一项强有力的、基于人群的病例对照研究，利用早期病例确定方法来自癌症登记处和经过测试的用于公正控制确定的最新科学方法。具有高从大约 600 名从不吸烟的女性 AA 肺癌病例和 600 名女性中收集的高质量、多层次数据种族和年龄频率匹配的对照，我们的目标是：目标 1a。确定 AA 女性中 LCINS 的危险因素，注意组织学和 EGFR（表皮生长因子受体）状态的差异（使用全外显子组测序[WES]），并关注多层次因素，包括：a）遗传血统； b) 个人—— 暴露水平，包括假定和可疑的风险因素； c) 环境层面的风险因素，包括室内以及环境空气污染物和社会环境，考虑到美国的出生日期和年份与亚洲;目标 1b。确定多级风险因素对 AA 中 LCINS 的独立和共同贡献女性，通过计算每个风险因素的单独和总体可归因风险；目标 2a。表征 AA 女性中 LCINS 的突变情况，通过配对肿瘤-正常组织样本的 WES 来定义 LCINS AA 女性的体细胞突变谱、突变特征和 EGFR 状态；和目标 2b。识别多与主要突变肿瘤特征相关的危险因素水平。所有目标都将通过以下方式评估潜在差异 EGFR 状态。拟议的研究将涉及收集最大的基于人群的肺癌病例—— 对照数据集，包含相关的遗传和肿瘤基因组数据，适用于从不吸烟的 AA 女性。它将提供第一个—— 有机会评估导致不同 AA 族裔肺癌差异的详细多层次因素组。清楚了解 AA 中肺癌风险较高且不断增加的病因从不吸烟的女性对于设计适当的预防策略以减轻她们的沉重负担是必要的疾病。