DNA Repair and Bladder Cancer

描述（由申请人提供）： 每年，美国有51，200人被诊断患有膀胱癌，10，600人死于这种疾病。暴露于环境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，与砷接触有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辩论的主题，其确切的作用机制仍然未知。此外，许多研究报告了吸烟、基因多态性和癌症风险之间的相互作用。我们将检验核苷酸切除修复途径的多态性与膀胱癌风险增加相关的假设。我们将使用在新罕布什尔州（850例病例，1,365例对照）进行的一项以膀胱癌为基础的大规模人群研究中收集的暴露数据和血液样本来解决这一假设。该项目的具体目标是：1）检验核苷酸切除修复途径基因（XPD，XPC，XPA和ERCC 1）中的遗传变异与膀胱癌风险增加相关的假设，2）确定环境暴露（砷，吸烟）和核苷酸切除修复多态性是否相互作用以增加膀胱癌风险。这项研究提供了一个独特的机会，以澄清遗传和环境因素如何影响DNA修复，并有助于膀胱癌的易感性。通过我们的研究，我们希望有助于我们对膀胱癌的机械理解，并确定可能具有更大环境诱发癌症风险的人群亚组。

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.