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

• 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
• 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

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.

摘要 从不吸烟者肺癌（LCINS）是一种不成比例地影响亚裔美国人（AA）的疾病和差异 女性与大多数种族/族裔群体中观察到的发病率下降趋势相反， 特别是腺癌，在大多数AA种族群体中一直在增加。大多数AA女性， 近90%的中国肺癌患者从不吸烟。人们所知甚少， 导致AA女性中LCINS发病率高且不断增加的风险因素，特别是风险 亚洲研究中确定的因素在AA人群中的意义可能有限。此外， 了解这一人群中肿瘤的突变特征与其 相关的风险因素。这些信息将提高我们对潜在的潜在机制的理解。 途径。因此，本研究的总体目标是确定已知、推定和疑似的可归因风险。 从不吸烟的AA女性中肺癌的危险因素认识到目前没有美国的数据集 也没有现有队列的数据来评估可能与此最相关的推定和疑似风险因素 人口，我们提出了一个强大的，以人口为基础的病例对照研究，利用早期病例确定方法 从癌症登记处和测试的国家的科学方法的无偏控制确定。高- 从估计600例女性AA从不吸烟者肺癌病例和600例女性AA从不吸烟者肺癌病例中收集的高质量、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的风险因素， 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]），并关注多水平因素，包括：a）遗传祖先; B）个体- 水平暴露，包括推定和怀疑的风险因素;以及c）背景水平风险因素，包括室内 环境空气污染物和社会环境，考虑到美国的出生和年份， 亚洲;目标1b。确定AA中多水平危险因素对LCINS的独立和联合贡献 女性通过计算每个风险因素的归因风险，单独和总共;目标2a.表征 AA女性中LCINS的突变景观，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;以及目标2b。识别多个- 与主要突变肿瘤特征相关的水平风险因素。所有目标将通过以下方式评估潜在差异： EGFR状态。这项拟议中的研究将涉及最大的人口为基础的肺癌病例的组装- 对照数据集，与相关的遗传和肿瘤基因组数据，为从不吸烟的AA妇女。它将提供第一个- 有机会评估导致不同AA种族肺癌差异的详细多层次因素 组清楚地了解AA中肺癌风险高和增加的病因学因素 从不吸烟的女性是必要的，以设计适当的预防策略，以减少他们的高负担， 疾病