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目的研究Ⅱ相代谢酶基因NQO1密码子187多态性与肺癌易感性的关系,分析吸烟与该多态性可能的交互作用。方法采用病例-对照研究,收集原发性肺癌患者396例为病例组,同时随机抽取465名当地健康居民作为对照组,进行流行病学调查。运用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法分析NQO1基因Pro187Ser位点的多态性。应用Logistic回归模型分析该位点多态性与肺癌易感性的关系。结果等位基因Pro和Ser在病例组的频率分别为50.88%和49.12%,在对照组中则分别为56.13%和43.87%,2组差异有统计学意义(P=0.0296)。携带Ser/Ser基因型者患肺癌,特别是肺腺癌的风险显著高于携带野生型Pro/Pro者,其OR值分别为1.53(95%CI=1.01~2.32)和2.16(95%CI=1.16~4.02)。携带纯合突变型Ser/Ser的吸烟者患肺癌的风险为携带至少1个野生等位基因的吸烟者的1.5倍。而NQO1基因的纯合突变型Ser/Ser与吸烟在肺腺癌的发病中存在显著的协同作用(OR=2.74,95%CI=1.00~7.49)。结论Ⅱ相代谢酶基因NQO1密码子187的多态性可能与肺癌的易感性有关。在肺癌的发生过程中,吸烟可能与该位点多态性存在协同作用。
Objective To study the relationship between the polymorphism of codon 187 of NQO1 gene and the susceptibility to lung cancer and to analyze the possible interaction between smoking and polymorphism. Methods A case-control study was conducted in which 396 patients with primary lung cancer were selected as case group and 465 healthy local residents were randomly selected as control group for epidemiological investigation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphism of Pro187Ser NQO1 gene. Logistic regression model was used to analyze the association between the polymorphism and the susceptibility to lung cancer. Results The frequency of allele Pro and Ser in case group was 50.88% and 49.12% respectively, while it was 56.13% and 43.87% respectively in the control group. The difference between the two groups was statistically significant (P = 0.0296). Patients with Ser / Ser genotype had a significantly higher risk of developing lung cancer, especially lung adenocarcinoma, than those with wild-type Pro / Pro, with ORs of 1.53 (95% CI = 1.01-2.32) and 2.16 (95% CI = 1.16 ~ 4.02). Smokers with homozygous mutant Ser / Ser are 1.5 times more likely to develop lung cancer than smokers who carry at least one wild-type allele. The homozygous mutant Ser / Ser of NQO1 gene had significant synergistic effect with smoking in the development of lung adenocarcinoma (OR = 2.74, 95% CI = 1.00-7.49). Conclusion The polymorphism of codon 187 of phase Ⅱ metabolic enzyme NQO1 may be related to the susceptibility of lung cancer. In the process of lung cancer, smoking may have a synergistic effect with the polymorphism at this locus.