肺癌易感性标记物与肺癌关系的病例对照研究

Case control study on relationship between lung cancer and its susceptibility marker

目的探讨谷胱甘肽转移酶(GST)和细胞色素CYP1A1、CYP2E1多态性与肺癌易感性的关系。方法用病例对照研究方法,收集广东籍新发原发性肺癌病人91例及同期非肺部疾患住院病人91例作对照,采用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测病例和对照的CYP1A1、CYP2E1和GSTM1基因多态性。结果CYP1A1突变型(m2m2)与野生型(mlml)比较,OR值1.51;CYP2E1C1C1型与C1C2型比较,OR值1.80;C2C2型与C1C2型比较,OR值5.48;GSTM1基因缺失型与正常型比较;OR值1.26。两种基因联合分析结果表明:GSTM1基因缺失并携带CYPlAlm2m2与GSTM1基因正常并携带CYP1A1m1m1者比较,OR值2.29,GSTM1基因缺失并携带CYP2E1C1C1型者与GSTM1基因正常并携带CYP2E1C1C2型者比较,OR值2.13,携带CYP1A1m2m2型以及CYP2E1C1C1型者与携带CYP1A1m1m1型和CYPE1c1c2型者比较,OR值3.00。3种基因联合作用分析结果表明:携带CYP1A1m2m2型以及CYP2E1C1C1型并且GSTM1基因缺失者比携带CYP1A1m1m1型和CYP2E1c1c2型且GSTM1基因正常者提高了患肺癌的危险性,OR值3.97。结论CYP1A1、CYP2E1和GSTM1在单因素分析中末显示出与肺癌风险的联系,2个基因和3种基因的联合作用似乎可以提高患肺癌的危险性,但无统计学意义。提示这3种基因均不是肺癌个体易感性的主效基因,可能是次效基因。

Objective To study the correlation of polymorphisms with CYP1A1,CYP2E1 RsaI and GSTM_1 independently and in corrbination with the risk of lung cancer.Methods A case control study which included 91 cases of lung cancer and 91 controls collected from the hospital.Blood samples were collected from all cases and controls for detecting CYP1A1,CYP2E1 RsaI and GSTM_1 polymorphisms which were analyzed by PCR and RELP.Results Compared with the m_1m_1 genotype of CYP1A1,OR of the m_2m_2 genotype of CYP1A1 was 1.51(0.76～3.01),OR of the m_1m_2 genotype of CYP1A1 was 0.84(0.41～1.72).Compared with the C_1C_2 genotype of CYP2E1,OR of the C_1C_1 genotype of CYP2E1 was 1.80(0.95-3.40),and those of the C_2C_2 genotype was 5.48(1.21～25.23).Comparing with the GSTM_1(+/+)genotype,OR of the GSTM_1(0/0) was 1.26(0.69-2.30).The results of analysis of the corrbination of two genetic polymerphisms showed that the people of CYP1A1 and GSTM_1 null(0/0) had 2.29(0.92～9.97) who carried out m_2m_2 genotype fold risk of developing lung cancer compared with those who carried out m_1m_1 genotype of CYP1A1 and GSTM_1(+/+) genetype.Compared with GSTM_1(+/+) genotype with C_1C_2 genotype of CYP2E1,OR of GSTM_1 null(0/0) with C_1C_1 genotype of CYP2E1 was 2.13(0.82～5.56).But there was no statistical significance(P>0.05).Compared with those carrying m_1m_1 genotype of CYP1A1 and C_1C_2 genotype of CYP2E1,the people with m_2m_2 genotype of CYP1A1 and the C_1C_1 genotype of CYP2E1 increased in risk of lung cancer,the OR was 3.00(1.03～8.78).The results of analysis of the corrbination of three genetic polymerphisms showed that people carrying m_2m_2 genotype of CYP1A1,C_1C_1 genotype of CYP2E1 and GSTM_1 null(0/0) had higher risk of lung cancer than those with the other genotypes of this three genetic polymerphisms,OR was 3.97(0.94～16.79).Conclusion Polymorphism of a single gene of CYP1A1,CYP2E1,and GSTM_1 was not associated with the risk of lung cancer.The corrbination of two or more genetic polymerphisms might increase the risk of lung cancer,but there was no statistic significance.The three gene polymorphisms investigated were of minor importance susceptibility markers for lung cancer in this population.