细胞色素P450和谷胱甘肽硫转移酶基因多态性与喉癌发生及临床预后的关系

Relationship between susceptibility and prognosis of laryngeal cancer and genetic polymorphisms in CYP1A1 and GSTM1

目的 探讨代谢酶细胞色素P4 5 0 (cytochromeP4 5 0 ,CYP1A1)和谷胱甘肽硫转移酶(glutathioneS transferase ,GSTM1)基因多态性与国人喉癌的发生及临床预后的关系。方法 采用病例 对照研究的方法 ,以 89例喉癌患者及 16 4例非癌对照者的外周血白细胞为样本 ,利用聚合酶链反应(polymerasechainreaction ,PCR)技术分析了Ⅰ相代谢酶CYP1A1和Ⅱ相代谢酶GSTM1基因多态性。结果 喉癌组中CYP1A1的 3种基因型野生型 (wild type ,W)、杂合型 (wildnee +mutation ,MW )、突变型(mutate type ,M)各占 37 1%、2 7 0 %、36 0 % ,明显高于对照组 (χ2 =12 30 ,P <0 0 5 )。喉癌组中GSTM1缺失 (- )基因型频率 (5 6 2 % )高于对照组 (χ2 =4 6 1,P <0 0 5 )。联合基因型CYP1A1与GSTM1基因多态性的比较 ,则携带CYP1A1W和GSTM1(- ) ,CYP1A1MW和GSTM1(- ) ,CYP1A1M和GSTM1非缺失 (+)基因型者患喉癌的风险度分别为 1 4 2 (95 %可信区间 0 6 2～ 3 2 2 ) ,1 6 7(95 %可信区间 0 7～ 4 0 3) ,2 5 5 (95 %可信区间 1 0～ 6 5 4 ) ,而携带CYP1A1M和GSTM1(- )基因型个体患喉癌的风险度最高 ,为 4 0 2 (95 %可信区间 1 6 5～ 9 79)。吸烟与喉癌的发生有关 ,CYP1A1突变型及GSTM1缺失型与吸烟有协同作用 ,并与发病时?

Objective To investigate the relationship between susceptibility and prognosis of laryngeal cancer and genetic polymorphisms in CYP1A1 and GSTM1. Methods The genetic polymorphisms of CYP1A1 exon-7 and GSTM1 were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of 89 laryngeal cancer cases and 164 non-cancer controls. Results Either in the frequency of CYP1A1(W,MW,M) and GSTM1 negative individual of laryngeal cancer were significantly higher than that in the controls( P <0.05). Combined genetype of CYP1A1 and GSTM1,that is CYP1A1 W/ GSTM1 (-),CYP1A1 MW/ GSTM1 (-),CYP1A1 M/GSTM1 (+),CYP1A1 M/GSTM1 (-) had higher risk than those combined genotypes,which ratios were 1.42 (0.62～3.22),1.67 (0.7～4.03),2.55 (1.0～6.54) and 4.02 (1.65～9.79),respectively. Statistic analysis suggested an interaction between smoking and CYP1A1 M/GSTM1 (-) genotypes polymorphisms which increase risk of laryngeal cancer. There was no significant difference in the frequency of CYP1A1,GSTM1 individual with the development and prognosis of laryngeal cancer. Conclusion The present datas suggested that genetic polymorphisms of CYP1A1 and GSTM1 were susceptible to laryngeal cancer. Individuals with CYP1A1 M or GSTM1 (-) had increased risk of developing laryngeal cancer,but individuals with combined CYP1A1 M/GSTM1 (-) and smoking were more susceptible. Genetic polymorphismsof CYP1A1 and GSTM1 are not related with clinic process of laryngeal cancer.