白细胞介素-28B基因多态性与原发性肝细胞肝癌的关系

Correlation between interleukin-28B genetic polymorphisms and primary hepatocellular carcinoma

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i1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％C／）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。

Objective 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 310 healthy 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 gender restrictions. 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 rs5803223 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 ease 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 statistieally 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%C1） 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 elinical data indicated that the frequeney 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.