Genetic Role of EGFR pathway in Interstitial Lung Disease

EGFR 通路在间质性肺疾病中的遗传作用

• 批准号: 7837627
• 负责人: Wanqing Liu
• 金额: $ 7.8万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-11 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7837627
• 关键词: Accounting; Alleles; Animal Model; Cancer Patient; Chronic; Development; Disease; Engineering; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Figs - dietary; Future; Gene Expression; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Variation; Goals; Human; Individual; Interstitial Lung Diseases; Investigation; Lung; Lung diseases; Malignant neoplasm of lung; Molecular Target; Pathogenesis; Pathway interactions; Play; Predisposition; Receptor Signaling; Regulation; Research; Risk; Role; Signal Transduction; Structure of parenchyma of lung; Testing; Tissues; Variant; abstracting; cell type; ethnic difference; genetic risk factor; genetic variant; insight; population based; prevent; public health relevance; sample collection

DESCRIPTION (provided by applicant): Background: Interstitial lung disease (ILD) encompasses a broad range of chronic lung disorders. The mechanisms of pathogenesis for the development of this disease are mostly unknown. It is widely believed that genetic factors play an important role in the development of interstitial lung disease (ILD). However, testable alleles accounting for common entities have not yet been discovered. Recently, administration of inhibitors for epidermal growth factor receptor (EGFR) has been shown to induce ILD in lung cancer patients with significant ethnic differences. The combination of this observation and evidence from genetically engineered animal models suggests that genetic variation related to EGFR contributes to the development of ILD. Our ultimate goal is to identify the genetic determinants of ILD through understanding the regulation of EGFR and its signaling by genetic polymorphisms. We have identified functional genetic variants in EGFR pathway genes. We hypothesize that these genetic variants in EGFR pathway genes may determine gene expression and modulate EGFR signaling in human lung, thus conferring susceptibility to ILD. To test our hypothesis, we propose studies utilizing the large disease sample collection from The Lung Tissue Research Consortium (LTRC). Specific Aims: 1) To conduct a population-based association study between functional variants in EGFR pathway genes and ILD; 2) To evaluate the correlation between the functional variants and gene expression of the EGFR pathway in ILD tissue; 3) To test the interaction between the functional variants and EGFR signaling activity in different cell types of ILD tissue. Significance: This investigation has the potential to identify the genetic risk factors of human ILD, and to provide insight into mechanisms important to the pathogenesis of the disease. PUBLIC HEALTH RELEVANCE: Project Narrative This study will test whether genetic variants within a group of genes related to the epidermal growth factor receptor (EGFR) increase the risk to develop interstitial lung disease (ILD). Understanding this could potentially help to identify the individuals who may develop the disease in the future and thus potentially prevent it. It will also help to identify molecular targets that could be used to develop better treatment for ILD. (End of Abstract)

描述（由申请人提供）：

项目成果

Epidermal growth factor receptor (EGFR) pathway genes and interstitial lung disease: an association study.

• DOI: 10.1038/srep04893
• 发表时间: 2014-05-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Li C;Wei R;Jones-Hall YL;Vittal R;Zhang M;Liu W
• 通讯作者: Liu W

Association between MUC5B and TERT polymorphisms and different interstitial lung disease phenotypes.

• DOI: 10.1016/j.trsl.2013.12.006
• 发表时间: 2014-05
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Wei R;Li C;Zhang M;Jones-Hall YL;Myers JL;Noth I;Liu W
• 通讯作者: Liu W