MOLECULAR EPIDEMIOLOGY OF HUMAN CANCER

肺癌是美国女性和男性癌症死亡的主要原因，其中约90%的死亡是由主动吸烟引起的。环境烟草烟雾（ETS）暴露被认为是不吸烟者患肺癌的重要危险因素。我们调查了一个假设，即从不吸烟的女性，暴露于ETS并患肺癌，是一个遗传易感人群。我们分析了106名从不吸烟的女性的存档肿瘤组织，这些女性参加了ETS和肺癌风险的病例对照研究。我们分析了癌症易感基因的生殖系多态性，这些基因激活，即，细胞色素p450 1A 1（CYP 1A 1），并解毒，即，谷胱甘肽S-转移酶M1（GSTM 1）和GSTT 1化学致癌物，在烟草烟雾中发现。在一项仅限于患者的分析中，将潜在易感等位基因相关的风险与累积ETS暴露相关的风险进行了比较，这是通过结构化访谈确定的。将未暴露于ETS的从不吸烟者（n=55）与暴露于ETS的从不吸烟者（n=51）进行比较，发现他们更可能缺乏谷胱甘肽S-转移酶M1（即，GSTM 1无效）活性（优势比= 2.6，95%置信区间= 1.1-6.1）。在暴露于55包-年ETS的人群中，随着ETS暴露量的增加（双侧P = 0.02），风险出现统计学显著上升趋势，达到超过6倍的超额风险。一种常见的遗传多态性将从不吸烟的人群分为两组，两组人数大致相等，一组（GSTM 1无效等位基因的纯合携带者）与另一组（野生型GSTM 1等位基因的杂合或纯合携带者）相比，ETS导致肺癌的风险在统计学上显著更高。本病例系列肺癌中p53突变谱的分析正在进行中。此外，我们已经启动了一项大型肺癌病例对照研究，以检查癌症风险的性别差异和诱变剂敏感性测定在预测癌症风险中的价值。- p，肿瘤抑制因子，氡，烟草烟雾，-人类受试者

Lung cancer is the leading cause of cancer death for American women and men, and approximately 90% of these deaths are caused by active cigarette smoking. Environmental tobacco smoke (ETS) exposure is considered a significant lung cancer risk factor for never-smokers. We investigated the hypothesis that never-smoking women, who are exposed to ETS and develop lung cancer, are a genetically susceptible population. Archived tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS and lung cancer risk. We analyzed germline polymorphisms in cancer susceptibility genes that activate, i.e., cytochrome p450 1A1 (CYP1A1), and detoxify, i.e., glutathione S-transferase M1 (GSTM1) and GSTT1 chemical carcinogens, found in tobacco smoke. In an analysis limited to patients, the risks associated with the potential susceptibility alleles were compared with that for cumulative ETS exposure, as was determined by a structured interview. Never-smokers without ETS exposure who developed lung cancer (n=55), were compared with the never-smokers with exposure to ETS who developed lung cancer (n=51), and were found more likely to be deficient in glutathione S-transferase M1 (i.e., GSTM1 null) activity due to a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6, 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P = 0.02) reaching more than a six-fold excess risk in those exposed to 55 pack-years of ETS. A common genetic polymorphism divides the population of never-smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele). The analysis of the p53 mutation spectrum in the lung cancers from this case series is in progress. In addition, we have initiated a large lung cancer case-control study to examine gender differences in cancer risk and the value of the mutagen sensitivity assay in predicting cancer risk. - p, Tumor Suppressor, Radon, Tobacco Smoke, - Human Subjects