Benzo[alpha]pyrene Diol Epoxide (BPDE) Sensitivity at 9*

描述（由申请人提供）： 这项拟定研究将建立在广泛的流行病学数据库和标本库的基础上，这些数据库和标本库来自一项正在进行的膀胱癌研究，题为“膀胱癌的遗传易感性：一种分子流行病学方法”（R01 CA74880，申请人：Xifeng Wu）。这项家长资助包括一个多学科的研究小组，他们在病例对照研究中使用分子流行病学方法，共同目标是确定烟草诱导的膀胱癌发生易感性的个体间差异。最近的证据表明，对苯并[（]芘二醇环氧化物（BPDE），苯并[（]芘（B[（]P），烟草烟雾的成分的代谢产物的敏感性，是一种体质现象，是几种烟草相关癌症，如肺癌，头颈癌和膀胱癌的危险因素。需要进一步阐明BPDE的分子靶点。染色体9p物质的丢失是膀胱癌中最常见的基因组改变之一。此外，9p21和p16的改变经常见于慢性吸烟者的上皮细胞。本研究的主要目的是：（1）。目的探讨BPDE诱发的膀胱癌患者外周血淋巴细胞（PBLs）9p21染色体畸变率是否高于与膀胱癌患者性别、年龄（5岁）和种族相匹配的正常对照组。我们的工作假设是，9p21 BPDE的敏感性可能反映了遗传的遗传易感性的特定位点的致癌物质在吸烟，染色体9p21可能是致癌物质的分子靶点在烟草烟雾中，和个人与这种畸变的膀胱癌的风险增加。2）。目的：检测50例膀胱癌患者尿中淋巴细胞自发性9p21畸变的发生率，以及淋巴细胞9p21畸变水平与相应尿标本是否存在相关性。我们的工作假设是PBL中的畸变准确地反映了靶组织中的变化。3）。通过整合流行病学资料和分子细胞遗传学资料，评估遗传标记与年龄、性别、吸烟状况和营养状况之间的关系。这些数据是在父母补助金中定期收集的。拟议的易感性标志物可能是有用的生物标志物，以确定高风险人群，然后可以针对密集的戒烟计划，并可以参加化学预防试验。

DESCRIPTION (provided by applicant): This proposed study will build upon the extensive epidemiologic database and specimen repository derived from an ongoing bladder cancer study entitled "Genetic Susceptibility to Bladder Cancer: A Molecular Epidemiologic Approach" (R01 CA74880, applicant: Xifeng Wu). This parent grant includes a multidisciplinary group of researchers using a molecular epidemiologic approach in a case-control study with the common goal of identifying inter-individual differences in susceptibility to tobacco-induced bladder carcinogenesis. Recent evidence has suggested that sensitivity to benzo[(]pyrene diol epoxide (BPDE), the metabolic product of benzo[(]pyrene (B[(]P), a constituent of tobacco smoke, is a constitutional phenomenon and is a risk factor for several tobacco-related cancers such as lung, head and neck, and bladder cancers. There is a need for further elucidation of the molecular targets of BPDE. Loss of chromosome 9p material is one of the most frequent genomic alterations in bladder cancer. In addition, alterations of 9p21 and p16 are frequently seen in the epithelial cells of chronic smokers. The specific aims of the proposed study are: 1). To determine whether BPDE-induced chromosome aberrations on 9p21 are more common in the cultured peripheral blood lymphocyte (PBLs) of 200 bladder cancer patients than those of 200 controls matched to the cases on sex, age ( 5 years) and ethnicity. Our working hypothesis is that 9p21 BPDE sensitivity may reflect inherited genetic susceptibility of a specific locus to carcinogens in tobacco smoking, that chromosome 9p21 may be the molecular target of carcinogens contained in tobacco smoke, and that individuals with such aberrations are at an increased risk for bladder cancer. 2). To determine frequency of spontaneous 9p21 aberrations occur in cells in urine from 50 cases of bladder cancer patients and whether there is a correlation between level of 9p21 aberrations in lymphocytes and corresponding urine samples. Our working hypothesis is that aberrations in PBLs accurately reflect changes in the target tissue. 3). To assess the associations between the genetic marker and age, sex, cigarette smoking status, and nutrition status by integrating epidemiologic data with the molecular cytogenetic data. These data are being routinely collected in the parent grant. The proposed susceptibility marker may be useful as biomarkers to identify high-risk populations that could then be targeted for intensive smoking-cessation programs and could be enrolled into chemoprevention trials.