肺癌易感性与Ⅱ相代谢酶基因多态性关系

Association between polymorphisms of phase Ⅱ metabolic gene NQO1 and susceptibility to lung cancer

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 explore the relationship between the polymorphisms of phaseⅡ metabolic gene NQO1 codon 187 and the susceptibility to lung cancer and to evaluate possible interaction between NQO1 and smoking with the risk of lung cancer. Methods A case-control study including 396 new diagnosed lung cancer cases and 465 healthy resident controls was conducted. The PCR-based restriction fragment length polymorphism（RLFP） technique was applied to analyze the NQO1 polymorphism at Pro187Ser loci. The data were analyzed with logistic regression model. Results The frequency of allele Pro and Ser in case group was 50. 88% and 49. 12% ,respectively; while in the control group,it was 56. 13% and 43. 87%. A statistical significant difference was observed （P = 0. 0296）. The carriers of Ser/Ser had higher risk of lung cancer than Pro/Pro carriers （adjusted odds ratio [ A OR ] = 1.53,95 % confidence interval [ 95 % CI] = 1.01 -2. 32 ）. Moreover,the carriers of Ser/Ser had a much higher risk of adenocarcinoma than Pro/Pro carriers（AOR = 2.16,95% CI = 1. 16 -4. 02）. The smokers who carded mutative genotype of Ser/Ser possessed a 1.5 times higher risk of lung cancer than the smokers who carried at least one wild allele Pro. Furthermore, significant synergistic effect was seen between smoking and mutative genotype of NQO1 （Ser/Ser） in the occurrence of adenocarcinoma（AOR = 2.74,95% CI = 1.00 -7.49）. Conclusion The results suggested that genetic polymorphism of phase Ⅱ metabolic gene NQO1 codon 187 might play an importam role in the development of lung cancer. Furthermore, smoking might hold synergistic effect with the polymorphisms of NQO1 codon 187 in the occurrence of lung cancer.