肺癌易感性与4种代谢酶基因多态性关系的研究

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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P4501A1(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Ile462Val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%CI1.197~3.236)、1.775倍(OR=1.775,95%CI1.226~2.568)、1.983倍(OR=1.983,95%CI1.260~3.121)。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CYP1A1 Ile462Val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。 Objective To investigate the relationship between the polymorphisms of four metabolic enzymes and susceptibility to lung cancer. Methods A case-control study was conducted. 209 patients with lung cancer were selected as the case group and 256 healthy controls were selected as the control group. PCR-RFLP was used to detect the gene of phase I metabolic enzyme Cytochrome P4501A1 (CYP1A1), phase Ⅱ metabolic enzyme glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) and epoxide hydratase (mEH) gene more State. Results The distribution frequencies of the pure and mutant Ile462Val locus of CYP1A1 gene, GSTM1 deletion type and the Tyr113His locus of the mEH gene in the case group and the control group were significantly different (P <0.05) The risk of developing lung cancer was 1.968 times (OR = 1.968, 95% CI 1.97-3.236), 1.775 times (OR = 1.775, 95% CI 1.226-2.568), 1.983 Times (OR = 1.983, 95% CI1.260 ~ 3.121). There was no significant difference in the distribution frequencies of CYP1A1 Msp1 locus, GSTT1 and mEH gene His139Arg polymorphism between cases and controls (P> 0.05). Logistic multivariate regression analysis showed that there was interaction between CYP1A1 Ile462Val mutation genotype and GSTM1 deletion genotype, CYP1A1 Ile462Val genotype and mEH Tyr113His mutation genotype in the development of lung cancer, and the risk of lung cancer in both genotype carriers Respectively, 4.86,3.27 (P <0.05). Conclusion The gene mutation and inter-gene interaction of metabolic enzymes are related to the increased risk of cancer in lung cancer, which play a role in the carcinogenesis of lung cancer.
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