IL-6和IL-1β单核苷酸多态性与非吸烟女性肺癌易感性的关系

Association of Genetic Polymorphisms in IL-6 and IL-1β Gene with Risk of Lung Cancer in Female Non-smokers

背景与目的白介素-6(interleukin-6,IL-6)和白介素-1β(IL-1β)是白介素家族中具有多功能生物活性的细胞因子。IL-6-634(rs1800796)和IL-1β-31(rs1143627)分别是IL-6基因和IL-1β基因上的两个常见多态位点,本研究旨在探讨IL-6-634位点和IL-1β-31位点单核苷酸多态性与非吸烟女性肺癌易感性的关系,并探讨环境危险因素与基因多态性交互作用对肺癌发病风险的影响。方法采用病例-对照研究方法,纳入非吸烟女性肺癌患者363例和对照370例。采用χ2检验比较各基因型、相关危险因素暴露在病例与对照之间分布的差异,以比值比(odds ratio,OR)及其95%可信区间(confidence interval,CI)表示相对危险度。采用非条件Logistic回归分析多态基因型与肺癌间相关性及其与危险因素的交互作用。结果 IL-6-634位点携带CG基因型的个体发生肺癌危险升高(OR=1.61,95%CI:1.19-2.19),CG或GG型携带者患肺癌的风险明显高于CC型的携带者(OR=1.48,95%CI:1.10-1.98);IL-1β-31位点携带CT或TT型的个体肺癌的发病风险要低于CC携带者,但差异无统计学意义。与携带IL-6-634 CC基因型且无油烟暴露者相比,既有油烟暴露同时携带CG或GG基因型的个体发生肺癌的危险升高(OR=2.45,95%CI:1.54-3.90),而与携带CC型且无结核病史者相比,既有结核病史并且携带CG或GG基因型的个体发生肺癌的危险升高(OR=2.44,95%CI:1.05-5.66)。结论 IL-6-634基因多态性与非吸烟女性肺癌易感性相关且与油烟暴露和结核病史同时存在能增加患癌风险。

Background and objective Interleukin-6（IL-6） and interleukin-1β（IL-1β）,known as multifunctional cytokines with high biological activity,play an important role in physiological and pathological responses such as inflammation,immune response and even tumors.There have been multiple polymorphism loci found in IL-6 gene and IL-1β gene.The aim of this study is to investigate the relationship between IL-6-643（C/G） and IL-1β-31（C/T） polymorphisms and lung cancer risk among female non-smokers and explore the interaction effects on lung cancer risk between this two polymorphisms and potential risk factors such as cooking oil fumes exposure and history of tuberculosis.Methods We performed a case-control study using 363 female lung cancer patients as cases and 370 healthy volunteers as controls.Genomic DNA was extracted from peripheral blood samples using classical phenol chloroform method.The genotyping of IL-6-634 or IL-1β-31 polymorphisms was performed using Taqman real time PCR technique by ABI7500.Two sided χ2 test was used to compare the distribution of the genotypes and risk factors between cases and controls.Unconditional Logistic regression analysis was performed to calculate the odds ratios（ORs） with 95% confidence intervals（CIs） for estimating the association between certain genotypes and lung cancer and exploring the interaction of risk factors and genetic polymorphisms.Results The risk of lung cancer was significantly higher in those with IL-6-634 CG genotype than those with CC genotype（OR=1.61,95%CI：1.19-2.19,P=0.002）.The CG or GG genotype carriers had an elevated risk of lung cancer than CC genotype carriers（OR=1.48,95%CI：1.10-1.98,P=0.01）.No significant association was observed between IL-1β-31 gene polymorphism and lung cancer risk.Compared with IL-6-634 CC genotype carriers with no cooking oil fumes exposure,a significant higher risk was found in individuals who were CG or GG genotype carriers with exposure to cooking oil fumes（OR=2.45,95%CI：1.54-3.90）.Compared with IL-6-634 CC genotype carriers with no history of tuberculosis,a significant elevated risk was found in individuals who were CG or GG genotype carriers with history of tuberculosis（OR=2.44,95%CI：1.05-5.66）.Conclusion Our results indicated that IL-6-634 polymorphism was associated with the risk of lung cancer risk in female non-smokers.Individuals with both IL-6-634 CG or GG genotype and exposure to cooking oil fumes had a higher risk of lung cancer.Also individuals with both IL-6-634 CG or GG genotype and history of tuberculosis had an elevated risk of lung cancer.