MOLECULAR EPIDEMIOLOGY OF HUMAN LUNG CANCER

分子流行病学的目标之一是识别个体， 高癌症风险。 致癌物暴露的分子剂量学 癌症易感基因的遗传性功能多态性是 个人风险的主要决定因素。 的突变谱 p53肿瘤抑制基因在肺癌中与男性不同， 女性表明肺癌可能存在性别差异 需要进一步调查敏感性。 p53突变 非恶性组织中的负荷可能是致癌物的分子剂量学 损害例如，248个突变型p53细胞的增加被发现在 溃疡性结肠炎供体的结肠上皮， 正常对照者 血清抗p53抗体已在癌症中检测到 患者，并且在某些情况下，在临床癌症之前被检测到。 美国正在进行人类肺癌的病例对照研究。 和中华人民共和国。 在NCI-University of马里兰州 我们的研究发现，结合CYP 2D 6 A基因分型， B和T突变可预测肺癌风险。谷胱甘肽-S- 转移酶M1（GSTM 1）和CYP 1A 1基因多态性进行了研究，但 未发现任何多态性与肺癌相关。 然而，等位基因频率和基因型频率的种族差异， found. 在同一人群中检测了尿致突变。 最近 吸烟与致突变性有关，非裔美国人更多 可能有致突变的尿液，尽管根据最近的 吸烟，该协会没有统计学意义。没有 尿液CYP 1A 1或GSTM 1遗传多态性的相关性 诱变 我们还研究了非吸烟人群患肺癌的风险 中国女性的癌症发病率与美国女性相似。为了 为了探索肺癌的分子流行病学，我们发起了一项 不吸烟的中国女性。 共168例病例和对照 已经收集起来了。 来自日本的证据表明， 基因多态性在不吸烟者中最大。 我们假设 这一组人群中，非吸烟者的癌症发病率很高， 将阐明癌症风险的遗传倾向。 到目前为止， 已完成CYP 1A 1、CYP 2 E1、GSTM 1、CYP 2D 6、APOE和 GST-T已经完成，数据正在分析中。

One of the goals of molecular epidemiology is to identify individuals at high cancer risk. Molecular dosimetry of carcinogen exposure and inherited functional polymorphisms of cancer susceptibility genes are the major determinants of an individual's risk. The mutational spectra of the p53 tumor suppressor gene differs in lung cancers from males and females indicating possible gender differences in lung cancer susceptibility that warrant further investigation. The p53 mutational load in nonmalignant tissues may be a molecular dosimetry of carcinogen damage. For example, an increase in 248 mutant p53 cells is found in the colonic epithelial of donors with ulcerative colitis when compared to normal controls. Serum anti-p53 antibodies have been detected in cancer patients and, in some cases, are detected prior to clinical cancer. Case-control studies of human lung cancer are being conducted in the U.S. and the Peoples Republic of China. In the NCI-University of Maryland study we have now found that the combination of genotyping for CYP2D6 A, B and T mutations is predictive of lung cancer risk. The glutathione-S- transferase M1 (GSTM1) and CYP1A1 genetic polymorphisms were studied, but no association of either polymorphism with lung cancer were found. However, racial differences in allelic and genotypic frequencies were found. Urinary mutagenesis was tested in this same population. Recent smoking was associated with mutagenicity and African-Americans were more likely to have mutagenic urine, although when adjusted for recent smoking, the association was not statistically significant. There was no association of the CYP1A1 or GSTM1 genetic polymorphisms urinary mutagenesis. We also have studied lung cancer risk among nonsmoking Chinese women, who have similar cancer rates as U.S. women. In order to explore the molecular epidemiology of lung cancer, we have initiated a study of nonsmoking Chinese women. A total of 168 cases and controls have been collected. Evidence from Japan indicates that the effect of genetic polymorphisms are greatest in nonsmokers. We have hypothesized that this cohort, where there are high cancer rates among nonsmokers, will elucidate genetic predispositions for cancer risk. Thus far, analyses have been completed for CYP1A1, CYP2E1, GSTM1, CYP2D6, APOE, and GST-T have been completed and the data is being analyzed.