MOLECULAR EPIDEMIOLOGY OF HUMAN CANCER

环境烟草烟雾和氡在美国产生分子特征 非吸烟者的肺癌。 越来越多的证据表明，环境致癌物质可以离开 P53抑癌基因遗传损伤的“指纹” 在人类肿瘤内。这些数据表明，特定的致癌物可能 通过具有说服力的突变特征直接与个体肿瘤相关联。 被动吸烟与肺癌的发生有关的几个因素 流行病学研究和环境保护局 二手烟在1992年12月被列为A类致癌物质。 该项目检查非吸烟者的人肺肿瘤组织 将二手烟暴露与基因突变联系起来的遗传证据 P53抑癌基因。具体假设包括：(I)频率 从G：C到T：A颠换与编码链偏差相关 暴露在被动烟雾中。(Ii)易感因素包括 GSTM1和CYP1A1基因将调节G：C到T：A的频率 变身。 氡在铀引起的肺癌中产生249 Met P53突变。 与我们最初报告的肺部P53突变谱不同 新墨西哥州铀矿工人的癌症和Bartsch等人的癌症， Taylor和他的同事在肺部观察到一个突变热点249met 中国铀矿工的鳞状细胞癌而不是腺癌 科罗拉多州。因此，我们启动了一项研究，直接测试 上述假设通过慢性暴露正常人的支气管 上皮细胞共受4Gy射线照射(相当于1460工作 水平月)高线性能量转移阿尔法辐射，然后 用基因突变试验检测P53基因突变 频率这项研究的曝光阶段已经完成。我们的 数据表明，249met p53突变不是被诱导的，而且 P53突变谱与我们观察到的谱一致 来自新墨西哥州的铀矿工。

Environmental Tobacco Smoke and Radon Produce Molecular Signatures in Lung Cancers from Nonsmokers. Increasing evidence shows that environmental carcinogens can leave "fingerprints" of genetic damage in the p53 tumor suppressor gene within human tumors. These data suggest that specific carcinogens may be linked directly to individual tumors by telltale mutation profiles. Passive smoking has been linked to lung cancer development by several epidemiologic studies, and the Environmental Protection Agency classified secondhand smoke as a Class A carcinogen in December 1992. This project examines human lung tumor tissues from nonsmokers for genetic evidence linking secondhand smoke exposure to mutations in the p53 tumor suppressor gene. Specific hypotheses include: (i) Frequency of G:C to T:A transversions with a coding strand bias will correlate with passive smoke exposure. (ii) Susceptibility factors including GSTM1 and CYP1A1 genotypes will modulate the frequency of G:C to T:A transversions. Radon Produces 249met p53 Mutation in Lung Cancers from Uranium. In contrast to our initial report of the p53 mutation spectrum in lung cancer from uranium miners in New Mexico and that of Bartsch et al., Taylor and coworkers observed a mutation hotspot 249met, in lung squamous cell carcinoma but not adenocarcinoma from uranium miners in Colorado. Therefore, we have initiated a study to directly test the above hypothesis by chronically exposing normal human bronchial epithelial cells to a total of 4 Gy dose (equivalent to 1460 working level months) of high linear energy transfer alpha radiation and then using the genotypic mutation assay to determine the p53 mutation frequency. The exposure phase of this study has been completed. Our data indicate that 249met p53 mutations are not induced and that the p53 mutation spectrum is consistent with the spectrum observed by us in the uranium miners from New Mexico.