硫酸基转移酶1E1基因单核苷酸多态性联合吸烟与肺癌易感性的关系

Relationship between single nucleotide polymorphism of sulfotransferase 1E1 associated with smoking and susceptibility to lung cancer

目的:研究硫酸基转移酶(sulfotransferase,SULT)1E1基因的单核苷酸多态性(single nucleotide polymorphism,SNP)联合吸烟与肺癌易感性的关系。方法:采用病例-对照研究,收集原发性肺癌患者351例和非肿瘤患者207例,应用AllGloTM探针结合实时荧光PCR方法分析肺癌组和对照组中SLUT1E1多态位点A-3037G(rs4149525)基因型分布情况,比较不同基因型联合吸烟与肺癌易感性的关系,以及对肺癌不同病理类型的影响。结果:肺癌患者A-3037G多态位点的AA、AG、GG基因型和A、G等位基因频率分布与对照组比较,差异无统计学意义(P>0.05)。吸烟≥30包年的野生型纯合子个体罹患肺癌的风险增加,调整比值比(odds ratio,OR)为2.307[95%可信区间(confidence interval,CI)为1.285～3.976,P<0.05];吸烟≥30包年携带突变等位基因G的个体患肺癌的风险可能增加,调整OR值为1.523(95%CI为0.987～2.961,P=0.05)。3种基因型联合吸烟(≥30包年)可能增加了罹患肺鳞癌的风险,AA和AG+GG基因型的OR值分别为5.983(95%CI为2.786～12.850,P<0.01)和2.750(95%CI为1.245～6.075,P<0.05);而突变等位基因G对不吸烟个体似乎具有保护作用,OR值为0.296(95%CI为0.101～0.864,P<0.05);A-3037G多态性联合吸烟对肺腺癌的发病风险没有显著影响。结论:SULT1E1基因启动子区A-3037G多态性联合吸烟可能对肺癌的发病风险有一定影响。

Objective:To investigate the association between the single nucleotide polymorphism(SNP) of sulfotransferase 1E1 with smoking conditions and the hereditary susceptibility to lung cancer.Methods:A case-control study was performed.Totally 351 lung cancer patients and 207 cancer-free controls were recruited from the Chinese population in Shanghai Pulmonary Hospital.The A-3037G(rs4149525) polymorphism was determined using AllGloTM probes combined with real-time fluorescence PCR.The difference in the frequency distribution of genotypes and alleles between lung cancer group and the control group was analyzed by chi-square test.The relationship between SLUT1E1 gene polymorphism combined with smoking conditions and the risk of lung cancer was analyzed and the effect of gene polymorphism on the different pathological classifications of lung cancer was determined.Results:The genotype(AA,AG,GG) and allele distribution of SULT1E1 A-3037G SNP in the patients with lung cancer was not significantly different compared with that in controls(P>0.05).Compared with never-smokers with wild homozygous genotype,wild homozygous genotyped smokers(≥30 pack·year of smoking) had increased risk of developing lung cancer [odds ratio(OR)=2.307,95% confidence interval(CI): 1.285-3.976,P<0.05);the carriers with mutated allele G and ≥30 pack·year of smoking tended to have increased risk of developing lung cancer(OR=1.523,95%CI: 0.987-2.961,P=0.053).The three genotypes combined with smoking(≥30 pack·year) increased the risk of developing squamous cell carcinoma(OR=5.983,95%CI: 2.786-12.850,P<0.01,for AA genotype;OR=2.750,95%CI: 1.245-6.075,P<0.05,for AG+GG genotypes).However,the mutation of allele G may have protective effect on nonsmokers against the risk of developing squamous cell carcinoma(OR=0.296,95%CI: 0.101-0.864,P<0.05).The polymorphism of A-3037G combined with smoking had no significant effect on lung adenocarcinoma.Conclusion:A-3037G polymorphism in the promoter region of SULT1E1 gene combined with smoking has certain effect on the risk of developing lung cancer.