Molecular Epidemiology and Lung Cancer: A Nested Case-Control Study

分子流行病学与肺癌：巢式病例对照研究

• 批准号: 7751877
• 负责人: FREDERICA P PERERA
• 金额: $ 40.33万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-08 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751877
• 关键词: Address; Affect; Albumins; Area; Binding; Biological Markers; Blood; Blood specimen; Cancer Control; Cardiovascular Diseases; Case-Control Studies; Cause of Death; Chronic Disease; Collaborations; Collection; Data; Deterioration; Diagnosis; Diagnostic; Dietary History; Disease; Early Diagnosis; Enrollment; Environmental Health; Health; Histology; Individual; Life; Malignant Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Measures; Methods; Mission; Molecular Epidemiology; National Institute of Environmental Health Sciences; Nested Case-Control Study; Non-Small-Cell Lung Carcinoma; Paper; Pattern; Peptides; Physicians; Positioning Attribute; Predisposition; Procedures; Process; Protein Fragment; Proteins; Proteomics; Protocols documentation; Publications; Quality Control; Research; Research Design; Research Personnel; Resolution; Risk; Sample Size; Sampling; Sensitivity and Specificity; Serum; Shipping; Ships; Smoking; Smoking Status; Specimen; Staging; Study of serum; Surface; Techniques; Testing; Time; United States National Institutes of Health; Universities; Validation; Work; burden of illness; cancer prevention; case control; cohort; design; follow-up; lung cancer screening; mass spectrometer; new technology; pre-clinical; prospective; protein expression; response; tool

DESCRIPTION (provided by applicant): The broad objective of the proposed study is the early detection of lung cancer through the identification of patterns of protein expression with the potential to identify early disease. The research "nests" a case-control study within the prospective Harvard Physicians Health Study (PHS) to determine whether biomarkers in blood of healthy individuals can detect early disease that would manifest itself years or decades later. Specific Aims: Our aims are to test the following hypotheses: 1) The baseline blood samples from subjects who later develop lung cancer (cases) will differ significantly with respect to their patterns of protein expression from samples of subjects who are followed for the same period of time and have the same smoking status at enrollment but do not develop lung cancer (controls), such that an "overall" discriminating pattern can be identified that has adequate sensitivity and specificity (>80%) to serve as a potential biomarker of early disease. 2) The baseline blood samples from subjects who later develop Non-Small Cell Lung Cancer (NSCLC) will differ significantly with respect to their patterns of protein expression from samples of controls, such that a "specific" discriminating pattern can be identified that has higher sensitivity and specificity (>85%) to serve as a potential biomarker of early NSCLC. While a number of studies have demonstrated the potential of proteomics in early detection of lung cancer, the sample sizes have been small, none have involved well characterized prospective cohorts, and the specific markers, when identified, have been inconsistent from study to study. None has systematically assessed biomarker validity in terms of the sensitivity and specificity of the patterns under different circumstances of time from blood draw to diagnosis, histology, stage, or smoking status. This research is an essential step in their validation as tools in early detection of lung cancer. Research design and methods: Baseline blood samples from 350 cases and 700 matched controls will be selected from stored "enrollment" samples from the PHS and analyzed for patterns of protein expression. Detailed smoking, environmental, health and dietary histories (baseline and follow-up) have been obtained on each subject. Preliminary studies have demonstrated the feasibility of this collaboration between Columbia University, Harvard University, and the NCI/FDA and have generated data directly supporting all of the research aims. Lung cancer is the leading cause of death from cancer in the U.S. and worldwide and claims over 162,000 lives every year in the U.S. The proposal fits within the mission of the NIH, NCI, and NIEHS to reduce the burden of illness and within the NCI's and NIEHS' strategic areas highlighted for advancement: cancer prevention, early detection and prediction, molecular epidemiology, and validation of new biomarkers of preclinical risk.

描述（由申请人提供）：拟议研究的主要目标是通过鉴定具有识别早期疾病潜力的蛋白质表达模式来早期检测肺癌。该研究在哈佛医师健康研究（PHS）前瞻性研究中“嵌套”了一项病例对照研究，以确定健康个体血液中的生物标志物是否能够检测出几年或几十年后出现的早期疾病。具体目的：我们的目标是测试以下假设：1）后来发展为肺癌的受试者（病例）的基线血液样本在蛋白质表达模式方面与跟踪相同时间段且入组时具有相同吸烟状况但未发展为肺癌的受试者（对照）的样本的蛋白质表达模式存在显着差异，从而可以识别具有足够敏感性和特异性的“总体”区分模式 (>80%) 作为早期疾病的潜在生物标志物。 2) 后来患上非小细胞肺癌 (NSCLC) 的受试者的基线血液样本与对照样本的蛋白质表达模式存在显着差异，因此可以鉴定出具有更高敏感性和特异性 (>85%) 的“特定”区分模式，作为早期 NSCLC 的潜在生物标志物。虽然许多研究已经证明了蛋白质组学在肺癌早期检测方面的潜力，但样本量很小，没有一项研究涉及特征明确的前瞻性队列，而且具体标记物在确定后，各个研究之间也不一致。没有人系统地评估生物标志物在从抽血到诊断、组织学、分期或吸烟状态的不同时间情况下模式的敏感性和特异性的有效性。这项研究是验证它们作为肺癌早期检测工具的重要一步。研究设计和方法：将从 PHS 存储的“登记”样本中选出 350 例病例和 700 例匹配对照的基线血液样本，并分析蛋白质表达模式。已获得每个受试者的详细吸烟、环境、健康和饮食史（基线和随访）。初步研究证明了哥伦比亚大学、哈佛大学和 NCI/FDA 之间合作的可行性，并生成了直接支持所有研究目标的数据。肺癌是美国和全世界癌症死亡的主要原因，每年在美国夺走超过 162,000 人的生命。该提案符合 NIH、NCI 和 NIEHS 减轻疾病负担的使命，也符合 NCI 和 NIEHS 强调推进的战略领域：癌症预防、早期检测和预测、分子流行病学以及临床前新生物标志物的验证。 风险。