Exploring Common Linkage Regions in Lung Cancer and COPD

探索肺癌和慢性阻塞性肺病的共同关联区域

• 批准号: 8132613
• 负责人: Michele L. Cote
• 金额: $ 13.29万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8132613
• 关键词: 12p; Affect; Bioinformatics; Cancer Etiology; Case-Control Studies; Cause of Death; Cessation of life; Chromosomes; Chromosomes, Human, Pair 6; Chronic Obstructive Airway Disease; DNA; Data; Development; Diagnosis; Discipline; Disease; Etiology; Family; Genes; Genetic; Genotype; Goals; Inherited; Knowledge; Larynx; Link; Lung; Lung Adenocarcinoma; Lung diseases; Malignant Neoplasms; Malignant neoplasm of larynx; Malignant neoplasm of lung; Malignant neoplasm of pharynx; Maps; Occupational; Pathway interactions; Population; Predisposition; Recording of previous events; Recruitment Activity; Relative (related person); Reporting; Research; Research Personnel; Resources; Respiratory physiology; Risk; Risk Factors; Survival Rate; Susceptibility Gene; Symptoms; Techniques; Technology; Testing; United States; Variant; Woman; cigarette smoking; follow-up; genetic analysis; genetic epidemiology; genetic linkage analysis; genetic variant; improved; insight; interest; novel; skills

DESCRIPTION (provided by applicant): Lung cancer and Chronic Obstructive Pulmonary Disease (COPD) are two of the most common and most deadly pulmonary diseases. There is no cure for COPD, and it represents the 4th leading cause of death in the United States. Lung cancer is the leading cause of cancer-related deaths in the US, and little improvement has been made in diagnosis or treatment, resulting in a dismal 15% five-year overall survival rate. The most important risk factor for both diseases is cigarette smoking; however, occupational factors and family history are also known to increase risk. Additionally, a personal history of COPD has consistently been shown to increase risk of lung cancer. To identify chromosomal regions that are inherited with disease, several groups have collected DMA from families with multiple affected relatives and performed linkage analyses. In COPD, a region on chromosomes 6q-ter has been associated with lung function and COPD. In lung cancer, a single linkage analysis reported evidence of linkage between a region also on chromosome 6q and lung, laryngeal and pharyngeal cancers. These linkage studies have identified regions of interest and may help future research pinpoint genes that are associated with both lung cancer and COPD. However, these regions are still quite large and encompass hundreds of genes, requiring further research to isolate susceptibility genes. The overall goal of this research plan is to investigate the importance of chromosome 6 on lung cancer and COPD development. We hypothesize that in addition to cigarette smoking, the similarities between COPD and lung cancer development arise from a common genetic pathway(s). We believe that using a variety of statistical techniques and newly available resources, such as the HapMap, will provide novel insight to the etiology of these conditions and potentially identify new targets to improve treatment and survival. This proposal describes a five-year research plan to acquire knowledge and skills to become an independent cancer researcher, with specialized skills in the analysis of genetic data. This project uses existing data and DNA from a case-control study of women with adenocarcinoma of the lung, including those with both lung cancer and COPD, lung cancer only, COPD only, and cancer and COPD-free controls. Additionally, a small number of COPD cases will be prospectively collected. The scope of this project encompasses several disciplines, including epidemiology, genetics, and bioinformatics.

描述（由申请人提供）：肺癌和慢性阻塞性肺疾病（COPD）是最常见，最致命的肺部疾病。 COPD无法治愈，它代表了美国第四大死亡原因。肺癌是美国与癌症相关的主要原因的主要原因，诊断或治疗方面几乎没有改善，导致15％的五年总生存率令人沮丧。两种疾病的最重要危险因素是吸烟。但是，已知职业因素和家族史也会增加风险。此外，COPD的个人病史始终被证明会增加肺癌的风险。为了鉴定疾病遗传的染色体区域，几个小组从具有多个受影响的亲戚的家族中收集了DMA，并进行了连锁分析。在COPD中，染色体6Q-TER上的区域与肺功能和COPD有关。在肺癌中，单个连锁分析报道了在6q和肺，肺，喉和咽癌上的区域之间联系的证据。这些连锁研究已经确定了感兴趣的区域，并可能有助于未来的研究指出与肺癌和COPD相关的基因。但是，这些区域仍然很大，并且包含数百个基因，需要进一步的研究以分离敏感性基因。该研究计划的总体目标是研究6染色体对肺癌和COPD发育的重要性。我们假设除了吸烟外，COPD和肺癌发展之间的相似性还来自常见的遗传途径。我们认为，使用各种统计技术和新近可用的资源（例如HAPMAP）将为这些疾病的病因提供新颖的见解，并有可能确定改善治疗和生存的新目标。该建议描述了一项五年的研究计划，以获得知识和技能，以成为一名独立的癌症研究者，并具有专门的遗传数据分析技能。该项目使用现有的数据和DNA，对肺腺癌女性的病例对照研究，包括患有肺癌和COPD的腺癌，仅肺癌，仅COPD，以及无COPD和COPD的对照组。此外，将有少数COPD案件被前瞻性收集。该项目的范围涵盖了几个学科，包括流行病学，遗传学和生物信息学。