原发性肝细胞癌与IL-2、IFN-γ基因多态性关系

Gene polymorphism of IL-2,IFN-gamma and primary hepatocellular carcinoma

目的探讨细胞因子IL-2基因-330T/G(rs2069762)位点和IFN-γ基因-1615C/T(rs2069705)、+5171A/G(rs2069727)位点单核苷酸多态性与原发性肝细胞癌(HCC)发生的关系。方法采用医院为基础的病例对照研究方法于2007年6月—2010年7月在广西医科大学第一附属医院和广西肿瘤医院收集784例HCC患者和同期在广西医科大学第一附属医院及广西区医院体检中心1 017名健康对照人群进行环境暴露调查;采用Taq-Man荧光定量PCR技术对上述位点进行分型,应用logistic回归模型分析组间基因-环境和基因-基因的交互作用。结果 IFN-γ的-1615C/T和+5171A/G位点存在连锁不平衡(D'=0.976,r2=0.549,P=2.22-16),单倍型CG在人群中发生频率<0.03,其他3种单倍型CA、TA、TG频率在病例组和对照组间分布差异均无统计学意义(P>0.05);IL-2-330T/G和IFN-γ-1615C/T、+5171A/G 3个位点的基因型在HCC患者和健康对照人群中分布差异均无统计学意义(P>0.05);吸烟、饮酒和携带HBV等环境暴露因素与-330T/G位点的突变基因G对HCC的发生有协同作用,交互作用指数S分别为1.38、1.50、1.03;吸烟、饮酒、有肝癌相关家族史和携带HBV等环境暴露因素与-1615C/T、+5171A/G位点的基因多态性在HCC患病风险中存在负交互作用;logistic回归分析结果表明,携带IL-2的-330T/G位点突变基因G并且同时携带IFN-γ的-1615C/T、+5171A/G位点的突变纯合子TT/GG能增加HCC患病风险(OR=1.84,95%CI=1.08～3.83)。结论 IL-2基因-330T/G和IFN-γ基因-1615C/T、+5171A/G位点多态性与环境暴露因素存在交互作用,基因-环境、基因-基因交互作用可能增加HCC发生风险。

Objective To explore the association of interleukin-2 （ IL-2 ） -330T/G （ rs2069762 ）, interferon gamma （IFN-γ） -1615 C/T（ rs2069705 ） and ＋ 5171A/G （ rs2069727 ） single nucleotide polymorphisms （ SNPs ） with the incidence of primary hepatocellular carcinoma（HCC）, and to provide the reference for HCC risk assessment. Methods A hospital-based case-control study was carried out. Totally 784 HCC patients from First Affiliated Hospital of Guangxi Medical University and Guangxi Cancer Hospital and 1 017 controls from Physical Examination Center of First Affiliated Hospital of Guangxi Medical University and Guangxi People＇ s Hospital were investigated with a environmental exposure questionnaire during June 2007-July 2010. TaqMan fluorescence quantitative PCR technology was adopted to detect the SNPs of the genes. The interactions of gene-environment and gene-gene were analyzed with logistic regression model. Results -1615C/T and ＋ 5171A/G of IFN-γ had linkage disequilibrium（ D＇=0. 976,r2 =0. 549,P =2.22 t6）.The frequency of haplotype CG was less than 0. 03 in the study population. CA, TA and TG had no statistically significant difference among the three groups（P 〉 0. 05 ）. There were no statistically significant differences in the polymorphisms of IL-2 -330T/G ,IFN-γ-1615C/T and ＋ 5171A/G between HCC patients and controls（ P 〉 0. 05 ）. The interactions of IL-2- 330T/G mutant allele G with smoking, alcohol drinking and carrying HBV were positive with the synergy indexes （S） of 1.38,1.50 ,and 1.03 ,respectively. The individuals carrying IL-2 -330T/G mutant gene G and both IFN-gamma-1615C/T and ＋ 5171A/G mutant homozygote （ TT and GG） had increased risk of HCC （ odds ratio = 1.84,95 % confidence interval：1. 08 -3.83 ）. Conclusion There are interactions among polymorphisms of IL-2 -330T/G and IFN-γ -1615C/T, ＋ 5171A/G and the environmental exposure. The gene-environment and gene-gene interaction may increase the risk of HCC.