代谢酶CYP1A1、CYP2D6基因多态性与肺癌易感性的病例对照研究

Case-control study for the relationship of CYP1A1 and CYP2D6 polymorphisms with the genetic susceptibility to lung cancer

目的探讨代谢酶CYP1A1基因MspⅠ位点多态性、CYP2D6*10等位基因C188T位点多态性与人群肺癌遗传易感性之间的相关性。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测86例广州市肺癌患者和86例对照的CYP1A1、CYP2D6基因多态性分布频率,分析基因多态性与肺癌遗传易感性之间的相关性。结果 CYP1A1基因CC、TC、TT在病例组的携带率分别为17.44%、38.37%、44.19%,对照组分别为12.79%、29.07%、58.14%。和TT组比较,CC和TC组OR值为1.79(OR95%CI:0.68～4.77)和1.74(OR95%CI:0.84～3.59);CYP2D6基因C188/C、C188/T、T188/T病例组的携带率分别为31.40%、38.37%和30.23%,对照组分别为44.19%、33.72%和22.09%,和T188/T组比较,C188/C、C188/T OR值为1.93(OR95%CI:0.83～4.48)、1.60(OR95%CI:0.75～3.44);CYP2D6与CYP1A1联合作用时,CYP1A1(CC+TC)型基因及CYP2D6(C188/C+C188/T)型基因者患肺癌的风险为2.75(1.06～7.20)。结论 CYP1A1、CYP2D6两种基因单独存在时未显示出与肺癌风险的联系,两种基因多态的联合作用明显提高了肺癌的危险性。

Objective To evaluate the correlation of CYP1A1 gene MspⅠ polymorphism and CYP2D6＊10 allele C188T polymorphism with the genetic susceptibility to lung cancer.Methods The distribution frequencies of CYP1A1 and CYP2D6 gene polymorphisms were detected in 86 lung cancer cases and 86 controls by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）,and the relationship between the genetic polymorphism and genetic susceptibility to lung cancer was also analyzed.Results The frequencies of CYP1A1 gene CC,TC and TT genotypes in case group were 17.44%,38.37% and 44.19%,but that were 12.79%,29.07% and 58.14% in control group.Compared with TT genotype,the odd ratios of TT and TC genotypes were 1.79（OR95%CI：0.68-4.77） and 1.74（OR95%CI：0.84-3.59）.The frequencies of CYP2D6 gene C188/C,C188/T and T188/T genotypes in case group were 31.40%,38.37% and 30.23%,but that were 44.19%,33.72% and 22.09% in control group.Compared with T188/T genotype,the odd ratios of C188/C and C188/T genotypes were 1.93（OR95%CI：0.83-4.48） and 1.60（OR95%CI：0.75-3.44）.The individuals with both CYP1A1（CC＋TC） genotypes and CYP2D6（C188/C＋C188/T） genotypes showed 2.75-fold increase of risk（OR95%CI：1.06-7.20）.Conclusion Single polymorphism of CYP1A1 and CYP2D6 does not show the risk of developing lung cancer,but the combination of two genetic polymorphisms significantly increases the risk of developing lung cancer.