摘要目的 探讨白细胞介素-28B(IL-28B)基因不同位点SNP与原发性肝细胞肝癌的关系.方法 以2001年11月至2010年4月就诊于桂林某医院和北京某医院的肝癌患者作为病例组,共300例,其中有139例患者具有完整的临床追踪资料；选取2009-2010年于上述两所医院中进行健康体检,且无肿瘤及慢性乙型肝炎疾病史者作为对照组,共310名；研究对象均为汉族,无年龄、性别限制.经知情同意,每名研究对象采集外周血2ml,采用质谱分析法对研究对象IL-28B基因rs12972991、rs8099917、rs12979860和rs4803223等位点SNP进行分析.结果 病例组rs12972991位点C等位基因、rs8099917位点G等位基因和rs4803223位点G等位基因频率分别是6.7％ (40/598)、7.9％ (47/598)、10.0％(59/588)；对照组分别为2.9％( 18/618)、4.1％(25/616)、3.6％(21/608),病例组均高于对照组,差异有统计学意义(x2值分别为9.542、7.858、20.736,P值均＜0.05)；携带上述等位基因可增加原发性肝细胞肝癌的患病风险[OR(95％CI)值分别为1.67(1.13 ～2.46)、1.49(1.08 ～2.06)、2.91(1.79～4.72)].病例组rs12972991位点AC+ CC基因型、rs8099917位点GT+GG基因型和rs4803223位点GA +GG基因型频率分别为13.0％ (39/299)、14.7％ (44/299)、19.0％(56/296)；对照组分别为5.8％ (18/309)、8.1％( 25/308)、6.6％ (20/304),病例组均高于对照组,差异有统计学意义(x2值分别为9.319、6.557、20.948,P值均＜0.05)；携带上述基因型可增加原发性肝细胞肝癌的患病风险[ OR(95％ CI)值分别为2.24(1.31～3.83)、1.81(1.14～2.88)、2.90(1.78～4.70)].对患者临床资料分析发现,出现门静脉癌栓的患者rs4803223位点GA +GG基因型频率为50.0％(13/26),高于AA基因型频率[21.1％ (23/109)],差异有统计学意义(x2=8.965,P=0.003).结论 IL-28B基因多态性与原发性肝细胞肝癌患病存在关联,其中携带rs4803223位点GA+ GG基因型可增加原发性肝细胞肝癌患者门静脉癌栓的发生风险.

abstractsObjective To explore the correlation between single nucleotide polymorphisms (SNPs)of interleukin-28B (IL-28B) gene and the susceptibility to primary hepatocellular carcinoma (HCC).Methods A total of 300 histologically confirmed HCC cases (from November 2001 to April 2010) and 310healthy controls with no history of chronic hepatitis B or hepatocellular carcinoma ( 2009 - 2010 ) were selected from a hospital in Guilin and a hospital in Beijing for this case-control study.139 HCC patients in the case group had complete clinical tracking data.All the subjects were Han Chinese,with no age or genderrestrictions.2 ml peripheral blood samples were drawn from each subject with informed consent.SNP of rs12972991,rs4803223,rs8099917 and rs12979860 four loci in IL-28B gene were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF).Results The frequencies of C allele at rs12972991,G allele at rs8099917 and G allele at rs4803223 were 6.7％ (40/598),7.9％ (47/598) and 10.0％ (59/588) respectively in case group; all higher than the corresponding frequencies in control group,separately 2.9％ (18/618),4.1％ (25/616) and 3.6％ (21/608).The differences were statistically significant ( x2 =9.542,7.858,20.736,P values all ＜ 0.05 ).The above alleles could increase the risk of HCC,and the OR ( 95％ CI) values were separately 1.67 ( 1.13 - 2.46 ),1.49(1.08-2.06) and 2.91(1.79-4.72).The genotype frequencies of AC+CC at rs12972991,GT+GG at rs8099917,GA + GG at rs4803223 were 13.0％ (39/299),14.7％ (44/299) and 19.0％ (56/296)respectively in case group; while the frequencies were lower in control group,separately 5.8％ ( 18/309),8.1％ (25/308) and 6.6％ (20/304).The differences were statistically significant ( x2 =9.319,6.557,20.948,P values all ＜ 0.05 ).These genotypes may increase the risk of HCC,and the adjusted OR (95％CI) values were 2.24 (1.31 -3.83),1.81 (1.14 -2.88) and 2.90 (1.78 -4.70),respectively.The stratified analysis of the clinical data indicated that the frequency of genotype GA + GG at rs4803223 was 50.0％ ( 13/26 ) in patients of tumor thrombosis in portal vein (TTPV),higher than the frequency of genotype AA ( 21.1％,23/109 ).The difference was statistically significant ( x2 =8.965,P =0.003).Conclusion The results suggested that IL-28B gene polymorphisms was correlated to the susceptibility to HCC in Chinese Han ethnic population.Among them,GA + GG genotype at rs4803223 could increase the risk of TTPV in HCC patients.