脂氧酶12 -183G＞A变异影响非小细胞肺癌发病风险

摘要: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。

The effect of LOX12 -183G>A on the risk of non-small cell lung cancer

Abstract: Objective This study sought to identify the effect of LOX12 -183G>A polymorphism on the development of non-small cell lung cancer (NSCLC). Methods A total of 956 patients with NSCLC and 994 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated by logistic regression. Results The frequencies of the -183GG, GA, AA genotypes were 20.8%, 53.6%, 25.6% in NSCLC patients and 26.8%, 52.2%, 21.0% in controls. Multivariate logistic regression analysis showed an increased risk of developing NSCLC for -183AA genotype carriers with OR(95%CI) of 1.53 (1.17~2.00) compared to that of GG genotype carriers. When stratified by smoking status, the OR of -183AA genotype for heavy smokers were 9.12 (95% CI: 5.07-16.41; P<0.001), more than the sum of the OR of -183AA genotype for nonsmokers (OR=2.03; 95% CI: 1.34-3.09; P=0.001) and the OR of 183GG genotype for heavy smokers (OR=6.84; 95%CI: 3.81-12.31; P<0.001). Conclusion LOX12 promoter -183 G>A polymorphism interacted with smoking status to contribute to the risk of NSCLC.