Genetic Susceptibility for Lung Cancer in African Americans

非裔美国人肺癌的遗传易感性

• 批准号: 7743910
• 负责人: Christopher I. Amos
• 金额: $ 39.8万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743910
• 关键词: 15q; 15q24; 15q25; 6p21; African; African American; Age; American Cancer Society; Architecture; Area; California; Cancer Biology; Cancer Center; Cancer Etiology; Caucasians; Caucasoid Race; Cessation of life; Chromosomes; Cisplatin; Data; Data Analyses; Death Rate; Dependence; Developed Countries; Developing Countries; Development; Doctor of Medicine; Ethnic group; Funding; Gender Role; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genome; Genomics; Genotype; Goals; Grant; Human; Incidence; Individual; Institutes; Joints; Lead; Linkage Disequilibrium; Location; Logistic Regressions; Machine Learning; Malignant neoplasm of lung; Metabolism; Methods; Modeling; Pattern; Play; Polymorphism Analysis; Population; Population Attributable Risks; Predisposition; Procedures; Recruitment Activity; Research; Risk; Risk Estimate; Role; Sampling; San Francisco; Scheme; Screening procedure; Single Nucleotide Polymorphism; Site; Smoker; Smoking; Survival Rate; TERT gene; Telomerase; Testing; Tobacco Use Cessation; Tobacco smoking; Universities; Validation; Variant; cancer genetics; cancer risk; case control; density; disorder risk; genetic variant; genome wide association study; high risk; improved; insight; interest; male; men; parent grant; sex; tool

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer death among African-Americans and this population has approximately 1/3 higher risk than Caucasians. Recently, collaborative studies that we and others have lead have identified regions on chromosomes 15q25, 5p15 and 6p21 that are highly significantly associated with lung cancer risk in Caucasians. The regions of association on chromosome 15q and 6p lie in areas of the genome that show very strong levels of linkage disequilibrium in Caucasians so that identifying the specific causal gene and causal variant(s) is problematic. In African- Americans, our preliminary study of the region on chromosome 15q25 shows a much more punctate pattern of linkage disequilbrium so that studies of the African-American population will provide a more precise localization of genetic variants. The preliminary data suggest the role of multiple genetic factors, but our initial studies conducted with a limited number of samples and SNPs are not yet sufficient to identify precisely the location(s) of causal variants. Our preliminary data show stronger effects on risks from SNPs on chromosomes 5p and 15q in African-Americans than in Caucasians. We therefore propose to genotype samples from three centers comprising over 1300 lung cancer cases and 1300 controls for 400 SNP loci in each of the three regions of interest. We will also genotype ancestry informative markers so that we can evaluate the ancestral background as a confounder. The first aim will perform dense SNP analysis in three genomic regions to sublocalize and characterize the impact on lung cancer risk in three genomic regions. The second aim will perform more detailed modeling to estimate joint effects of smoking, sex and genetic factors on lung cancer risk. This analysis will allow us to identify groups of African-American individuals at particularly higher risks for developing lung cancer.

描述（由申请人提供）：肺癌是非洲裔美国人癌症死亡的主要原因，该人群的风险比白人高约1/3。最近，我们和其他人领导的合作研究已经确定了染色体15 q25，5 p15和6p 21上与高加索人肺癌风险高度相关的区域。染色体15 q和6p上的关联区域位于在高加索人中显示非常强的连锁不平衡水平的基因组区域，使得鉴定特定的致病基因和致病变体是有问题的。在非裔美国人中，我们对染色体15 q25区域的初步研究显示了一种更点状的连锁不平衡模式，因此对非裔美国人群体的研究将提供更精确的遗传变异定位。初步数据表明多种遗传因素的作用，但我们用有限数量的样本和SNP进行的初步研究还不足以精确识别因果变异的位置。我们的初步数据显示，非洲裔美国人染色体5 p和15 q上的SNP对风险的影响比高加索人更大。因此，我们建议对来自三个中心的样本进行基因分型，这些样本包括超过1300例肺癌病例和1300例对照，在三个感兴趣的区域中的每个区域中有400个SNP位点。我们还将对祖先信息标记进行基因分型，以便我们可以将祖先背景作为混杂因素进行评估。第一个目标是在三个基因组区域进行密集SNP分析，以亚定位和表征三个基因组区域对肺癌风险的影响。第二个目标将进行更详细的建模，以估计吸烟，性别和遗传因素对肺癌风险的联合影响。这项分析将使我们能够识别出患肺癌风险特别高的非裔美国人群体。