Exploring Common Linkage Regions in Lung Cancer and COPD

描述（申请人提供）：肺癌和慢性阻塞性肺疾病（COPD）是两种最常见和最致命的肺部疾病。慢性阻塞性肺病无法治愈，它是美国第四大死亡原因。肺癌是美国癌症相关死亡的主要原因，在诊断和治疗方面几乎没有取得任何进展，导致五年总生存率只有15%。这两种疾病最重要的危险因素是吸烟；然而，职业因素和家族史也会增加风险。此外，慢性阻塞性肺病的个人病史一直被证明会增加患肺癌的风险。为了确定遗传疾病的染色体区域，几个研究小组从有多个患病亲属的家庭中收集了DMA，并进行了连锁分析。在COPD中，染色体6q-ter上的一个区域与肺功能和COPD相关。在肺癌中，一项单连锁分析报告了6q染色体上的一个区域与肺癌、喉癌和咽癌之间存在连锁的证据。这些关联研究已经确定了感兴趣的区域，并可能有助于未来的研究确定与肺癌和COPD相关的基因。然而，这些区域仍然相当大，包含数百个基因，需要进一步研究以分离易感基因。本研究计划的总体目标是研究6号染色体在肺癌和慢性阻塞性肺病发展中的重要性。我们假设，除了吸烟，慢性阻塞性肺病和肺癌发展之间的相似之处源于共同的遗传途径。我们相信，利用各种统计技术和新的可用资源，如HapMap，将为这些疾病的病因提供新的见解，并有可能确定新的靶点来改善治疗和生存率。该提案描述了一个五年的研究计划，以获得知识和技能，成为一名独立的癌症研究人员，具有分析基因数据的专业技能。该项目使用了来自肺腺癌女性病例对照研究的现有数据和DNA，包括肺癌和COPD、仅肺癌、仅COPD以及癌症和非COPD对照。此外，还将前瞻性地收集少量COPD病例。该项目的范围包括几个学科，包括流行病学、遗传学和生物信息学。

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.