Molecular epidemiologic study on lung cancer susceptibility

细胞色素P4501 A1（CYP 1A 1）和谷氨酰胺S-转移酶（GST）被认为对苯佐（a）吡啶（BP）和香烟烟雾中的其他多环芳香氢化合物的激活或激活负有责任。我们在189磅癌症患者中检测了CYP 1A 1（Msp I和Ile-Val）和GSTs （M1和T1）的多态性。我们也测量了CYP 1A 1（烯基氢氧化酶， AHH）中的表型活性。在年龄、香烟剂量和年龄调整的AHH活性和历史类型的季节之间没有关系。在Msp I多态性中，基因型C的调节AHH诱导性（几何平均值和95%置信区间（CI） ; 17.8和114.0-22.7）明显高于其他两种基因型（P<0.0001），而在基因型A （5.0和6.0）和B （5.5和4.7-6.4）之间没有明显的差异。用另一只手，基因型Val/Val的非诱导AHH活动（0.141和0.105- 0.190 pmol/min/10-D16-D1细胞）异黄酮（伊尔-瓦尔）中的多态性明显高于那些基因型伊尔/伊尔（0.035 and 0.030-0.41 pmol/min/10型D16型D1 cells） and Ile/Val （0.034 and 0.027-0.43 pmol/min/10型D16型D1 cells） （P<0.0001）。不响应于历史学类型、TNM阶段、CYP 1A 1基因型或GSTM 1基因型、芳香-DNA添加水平是不可区分的。与高AHH诱导性相关的Msp I站点的变异基因型与IL-Val多态性中的变异基因型明显相关，加剧了CYP 1A 1催化活性的水平。这个与肺癌患者之间的关联比以前报告的健康控制要严重得多。

Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs) are considered to be responsible for the activation or inactivation of benzo(a)pyrene (BP) and other polycyclic aromatic hydrocarbons in cigarette smoke to carcinogens. We investigated polymorphisms of CYP1A1 (Msp I and Ile-Val) and GSTs (M1 and T1) in 189 lung cancer patients. We also measured phenotypic activity of CYP1A1(aryl hydrocarbon hydroxylase, AHH) in peripheral mitogen-treated lymphocytes.No relationship was observed between age-, cigarette dose- and season of the year-adjusted AHH activity and histologic type of tumor or TNM stage. Adjusted AHH inducibility of genotype C (geometric mean and 95% confidence interval (CI) ; 17.8 and 114.0-22.7) in Msp I polymorphism was significantly higher than those of the other two genotypes (P<0.0001), while no significant difference was observed between genotypes A (5.0 and 6.0) and B (5.5 and 4.7-6.4). On the other hand, non-induced AHH activity of genotype Val/Val (0.141 and 0.105-0.190pmol/min/10ィイD16ィエD1 cells) in isoleucinevaline (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.035 and 0.030-0.41 pmol/min/10ィイD16ィエD1 cells) and Ile/Val (0.034 and 0.027-0.43 pmol/min/10ィイD16ィエD1 cells) (P<0.0001). Irrespective of histologic type, TNM stage, CYP1A1 genotype or GSTM1 genotype, aromatic-DNA adduct levels were not distinguishable.Variant genotype at the Msp I site associated with high AHH inducibility, while variant genotype in Ile-Val polymorphism was significantly related to increased the level of CYP1A1 catalytic activity. This association among lung cancer patients was more exaggerated than healthy controls reported previously.