DNA Repair and Bladder Cancer

DNA 修复和膀胱癌

• 批准号: 6761816
• 负责人: Angeline Sanderson Andrew
• 金额: $ 7.9万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6761816
• 关键词: DNA repair; arsenic; bladder neoplasm; cancer registry /resource; cancer risk; clinical research; environment related neoplasm /cancer; gene environment interaction; genetic polymorphism; genetic susceptibility; human subject; interview; neoplasm /cancer epidemiology; neoplasm /cancer genetics; skin derivative; smoking; transcription factor

DESCRIPTION (provided by applicant): Each year, 51,200 people in the United States are diagnosed with bladder cancer and 10,600 die of the disease. Exposure to environmental chemicals as well as genetic factors play a significant role in initiation of bladder cancer. Epidemiologic investigations have clearly shown an increased risk of bladder and other cancers associated with arsenic exposure, but the level at which it poses a measurable health risk has been the topic of considerable debate, and its precise mechanism of action remains unknown. Furthermore, a number of studies have reported an interaction between smoking, genetic polymorphisms and cancer risk. We will test the hypothesis that polymorphisms in the nucleotide excision repair pathway are associated with increased bladder cancer risk. We will address this hypothesis using exposure data and blood samples collected in a large population-based study of bladder cancer in the New Hampshire (850 cases, 1,365 controls). The specific aims of the project will be to 1) test the hypothesis that genetic variants in the nucleotide excision repair pathway genes (XPD, XPC, XPA, and ERCC1), are associated with increased risk of bladder cancer, and 2) determine whether environmental exposures (arsenic, smoking) and nucleotide excision repair polymorphisms interact to increase bladder cancer risk. This study presents a unique opportunity to clarify how genetic and environmental factors affect DNA repair and contribute to bladder cancer susceptibility. Through our study, we hope to contribute to both our mechanistic understanding of bladder cancer and to identify subgroups of the population that may be at greater risk of environmentally-induced cancers.

描述(由申请人提供)： 在美国，每年有51,200人被诊断出患有膀胱癌，10,600人死于这种疾病。暴露于环境中的化学物质以及遗传因素在膀胱癌的发生中起着重要作用。流行病学调查清楚地表明，与砷暴露相关的膀胱癌和其他癌症的风险增加，但它构成可测量的健康风险的水平一直是相当大的争论的主题，其确切的作用机制仍不清楚。此外，许多研究报告了吸烟、基因多态和癌症风险之间的相互作用。我们将验证核苷酸切除修复途径的多态与膀胱癌风险增加相关的假设。我们将使用暴露数据和在新汉普郡一项基于人群的大型膀胱癌研究中收集的血液样本来解决这一假设(850例病例，1365名对照)。该项目的具体目标将是1)检验核苷酸切除修复途径基因(XPD、XPC、XPA和ERCC1)的遗传变异与膀胱癌风险增加相关的假设，以及2)确定环境暴露(砷、吸烟)和核苷酸切除修复基因多态是否交互作用增加膀胱癌风险。这项研究提供了一个独特的机会来阐明遗传和环境因素如何影响DNA修复并促进膀胱癌的易感性。通过我们的研究，我们希望有助于我们对膀胱癌的机制的理解，并确定人群中可能存在更高风险的环境诱发癌症的亚群。