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目的探讨位于脂氧酶12(LOX12)基因启动子区-183G>A单核苷酸多态与非小细胞肺癌发病风险之间的关系。方法选取非小细胞肺癌患者956例及健康对照994例,利用PCR-限制性片段长度多态性方法进行基因分型,以多变量Logistic回归分析比值比(OR)及其95%可信区间(95%CI)。结果 LOX12-183GG、GA、AA各基因型频率在病例组分别是20.8%、53.6%、25.6%,在正常对照组分别为26.8%、52.2%、21.0%。与-183GG基因型相比,AA基因型明显增加非小细胞肺癌的发病风险,其OR(95%CI)为1.53(1.17~2.00);而GA基因型并不增加非小细胞肺癌发病风险,其OR(95%CI)值为1.23(0.98~1.55)。吸烟分层分析显示,以携带-183GG基因型的不吸烟者为参照,携带-183AA基因型的重度吸烟者发生非小细胞肺癌的风险为9.12(95%CI:5.07~16.41,P<0.001),大于不吸烟但携带-183AA基因型者的OR值(OR=2.03,95%CI:1.34~3.09,P=0.001)与重度吸烟但携带-183GG基因型OR值(OR=6.84,95%CI:3.81~12.31,P<0.001)之和。结论 LOX12基因启动子区-183G>A单核苷酸多态可与吸烟交互作用共同增加非小细胞肺癌发病风险。
Objective To investigate the relationship between -183G> A single nucleotide polymorphism (SNP) located in the promoter region of lipoxygenase 12 (LOX12) gene and the risk of non-small cell lung cancer. Methods 956 non-small cell lung cancer patients and 994 healthy controls were selected for genotyping by PCR-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression analysis was used to analyze odds ratio (OR) and its 95% confidence interval 95% CI). Results The frequencies of LOX12-183GG, GA and AA genotypes were 20.8%, 53.6% and 25.6% in the case group and 26.8%, 52.2% and 21.0% in the normal control group, respectively. Compared with the -183GG genotype, the AA genotype significantly increased the risk of NSCLC (OR = 95% CI 1.53 (1.17-2.00)). However, GA genotype did not increase the risk of NSCLC, The OR (95% CI) value was 1.23 (0.98 to 1.55). Stratified analysis of smoking showed that the risk of developing non-small cell lung cancer was 9.12 (95% CI: 5.07 to 16.41, P <0.001) in heavy smokers with the -183AA genotype as compared to non-smokers with the -183GG genotype (OR = 2.03,95% CI: 1.34 ~ 3.09, P = 0.001) and those with heavy smoking but with -183GG genotype (OR = 6.84, 95% CI : 3.81 ~ 12.31, P <0.001). Conclusion The interaction of -183G> A single nucleotide polymorphism in LOX12 promoter and smoking may increase the risk of non-small cell lung cancer.