河南省人群五种基因多态性与肺癌易感性的关系

Association between genetic polymorphism of metabolizing enzymes and DNA repairing enzymes and the susceptibility of lung cancer in Henan population

目的探讨河南省人群中外源性化合物代谢酶CYP1A1、GSTM1、GSTT1、mEH和DNA修复酶XRCC1基因多态性与肺癌易感性的关系。方法采用病例-对照研究的方法,选取河南省209例肺癌患者为病例组,256例健康体检者为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测I相代谢酶基因CYP1A1,II相代谢酶基因GSTM1、GSTT1、mEH及DNA修复酶基因XRCC1的多态基因型。结果河南省人群中GSTM1缺失型,CYP1A1-exon7、mEH-exon3、XRCC1-194及XRCC1-280基因纯和突变型在病例组与对照组中的分布频率差异均有统计学意义(P<0.05),GSTM1基因缺失者与GSTM1基因阳性者相比发生肺癌的危险性升高(ORadj=1.76,95%CI:1.21-2.56,P=0.005);携带CYP1A1-exon7 Ile/val+val/val基因型的个体较携带CYP1A1-exon7 Ile/Ile基因型的个体发生肺癌的危险性升高(ORadj=1.65,95%CI:1.16-2.39,P=0.009);mEH-exon3突变基因型携带者与野生纯合型的个体相比发生肺癌的危险性升高(ORadj=1.77,95%CI:1.18-2.64,P=0.007);携带XRCC1-194 Arg/Trp+Trp/Trp基因型的个体较携带XRCC1-194 Arg/Arg基因型的个体发生肺癌的危险性升高(ORadj=1.55,95%CI:1.07-2.27,P=0.016);XRCC1-280 His/His基因型携带者较XRCC1-280 Arg/Arg+Arg/His基因型携带者发生肺癌的危险性升高(ORadj=2.21,95%CI:1.05-4.52,P=0.026)。CYP1A1-Msp1、GSTT1、mEH-exon4及XRCC1-399多态基因型在病例组与对照组中的分布频率差异均无统计学意义(P>0.05)。结论河南省人群中CYP1A1、GSTM1、GSTT1、mEH和XRCC1基因的分布与国内外相关报道有一定差异,其中CYP1A1-exon7、GSTM1、mEH-exon3、XRCC1-194及XRCC1-280基因位点的变异与河南省人群肺癌患癌危险度增高有关。

Objective To investigate the association between genetic polymorphism of metabolizing enzymes and DNA repairing enzymes and the susceptibility of pulmonary cancer in Henan population.Methods A case-control study of 209 lung cancer patients and 256 healthy control subjects was conducted in Henan population to investigate the role of CYP1A1-Msp1,CYP1A1-exon7,GSTM1,GSTT1,mEH-exon3,mEH-exon4 and XRCC1 in lung cancer.Genotyping was performed by using PCR based restriction fragment length polymorhphism techniques.Results The frequency of GSTM1-null,CYP1A1-exon7 mt/mt,mEH-exon3 mt/mt,XRCC1-194 Trp/Trp,XRCC1-280 His/His genotype in the lung cancer case group was significantly higher than that in control group（P0.05）.The risk of lung cancer was higher in individuals carrying genotypes of GSTM1（ORadj =1.76,95%CI 1.21~2.56,P=0.005）,CYP1A1-exon7 Ile/val＋val/val（ORadj=1.65,95%CI 1.16~2.39,P=0.009）,mEH-exon3 wt/mt＋ mt/mt（ORadj =1.77,95%CI 1.18~2.64,P=0.007）,XRCC1-194 Arg/Trp ＋ Trp/Trp（ORadj=1.55,95%CI 1.07~2.27,P=0.016） and XRCC1-280 His/His（ORadj=2.21,95%CI 1.05~4.52,P=0.026） than those carrying genotypes of GSTM1 null,CYP1A1-exon7 Ile/Ile,mEH-exon3 wt/wt,XRCC1-194 Arg/Arg and XRCC1-280 Arg/Arg＋Arg/His;There was no significant difference for CYP1A1-Msp1,GSTT1,mEH-exon4,XRCC1-399 genotype between the two groups（P0.05）.Conclusion The genetic polymorphisms of CYP1A1-exon7,GSTM1,mEH-exon3,XRCC1-194 and XRCC1-280 might contribute to the risk of developing lung cancer in Henan population.