肺癌易感性与4种代谢酶基因多态性关系的研究

目的 探讨4种代谢酶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,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相代谢酶基因细胞色素P450 1A1 (CYP1A1),Ⅱ相代谢酶基因谷胱甘肽S-转移酶M1 (GSTM1)、谷胱甘肽S-转移酶T1 (GSTT1)及环氧化物水化酶(mEH)基因的多态性.结果 CYP1A1基因Ⅱe462Val位点纯和突变型、GSTM1缺失型、mEH基因Tyr113His位点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),这3种变异基因型携带者与野生型携带者相比发生肺癌危险度分别为1.968倍(OR=1.968,95％CI 1.197～3.236)、1.775倍(OR=1.775,95％CI1.226～2.568)、1.983倍(OR=1.983,95％CI 1.260～3.121).CYP1A1基因Msp1位点、GSTT1及mEH基因His139Arg位点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).Logistic多元回归分析表明CYP1A1Ile462Val突变基因型与GSTM1缺失型、CYP1A1 Ile462Val突变基因型与mEH Tyr113His突变基因型之间在肺癌的发生中具有交互作用,这两种联合基因型携带者患肺癌的危险度分别为4.86、3.27 (P＜ 0.05).结论 代谢酶基因变异及基因间的交互作用与肺癌患癌危险度增高有关,其在肺癌的发生过程中起一定作用.

The relationship between genetic polymorphism of four metabolizing enzymes and susceptibility to lung cancer

OBJECTIVE To study the relationship between the polymorphism of four metabolizing enzymes and susceptibility to pulmonary cancer.METHODS A case-control study of 209 lung cancer patients and 256 control subjects was conducted to investigate the role of cytochrome P450 1A1(CYP1A1),glutathione S-transferase M1(GSTM1),glutathione S-transferase T1(GSTT1)and microsomal epoxide hydrolase(mEH)in lung cancer.Genotyping was performed using PCR based restriction fragment length polymorhphism techniques.RESULTS The frequency of CYP1A1 Val/Val,GSTM1-null and mEH His/His genotype in case group was significantly higher than that in control group(P﹤0.05),with the OR for lung cancer being 1.968(OR = 1.968,95%CI 1.197-3.236),1.775(OR = 1.775,95%CI 1.226-2.568),1.983(OR = 1.983,95%CI 1.260-3.121),respectively.There was no significant difference for CYP1A1-Msp1,GSTT1,mEH His139Arg genotype between the two groups(P﹥0.05).Synergistic effects were found between CYP1A1 Val/Val and GSTM1-null,CYP1A1 Val/Val and mEH His/His genotype.CONCLUSION These findings support the hypothesis which the polymorphism of metabolizing enzymes genes and their synergistic effects do contribute to the risk of developing lung cancer.