COX-2基因单核苷酸多态性与肝细胞癌关联的研究

Association of COX-2 gene SNPs with the risk of hepatocellular carcinoma

目的：探讨广西地区COX-2基因-1195G〉A（rs689466）和8473T〉C（rs5275）位点单核苷酸多态性与肝细胞癌（HCC）遗传易感性的关系。方法：采用以医院为基础的病例对照研究方法。研究对象为780例经组织学确诊的HCC患者和780例相同地区、年龄、性别和民族频数匹配的非肿瘤患者。运用TaqManMGB探针等位基因分型技术进行COX-2基因单核苷酸多态性的检测，以X^2检验和非条件Logistic回归模型分析比较病例和对照两组间各位点基因型频率分布的差异及其与HCC患病风险的关系，并进一步探讨基因-环境的交互作用对HCC患病风险的影响。结果：COX-2基因单位点-1195G〉A或8473T〉C多态与HCC患病风险无统计学相关性（显性模型下SNP-1195G〉A：校正OR-1．32，95％CI：0．94～1．85；SNP8473T〉C：校正OR-0．87，95％CI：0．64～1．18）。分层分析显示，显性模型下COX-2基因-1195G〉A位点GA＋AA基因型增加年龄〈55岁者患HCC的风险（校正OR=1．56，95％CI：1．03～2．37），而8473T〉C位点TC＋CC基因型可降低女性患HCC的风险（校正OR=0．50，95％CI：0．25～0．99）。进一步交互作用分析显示，COX-2基因-1195G〉A位点与年龄、8473T〉C位点与性别分别存在交互作用（P=0．002；P=0．007）。结论：COX-2基因-1195G〉A或8473T〉C位点SNP的单独效应可能与HCC易感性无关联，但是-1195G〉A与年龄、8473T〉C位点与性别存在交互作用，影响HCC的患病风险。

OBJECTIVE：To explore the relationship of COX-2 polymorphisms -1195G〉A （rs689466） and 8473T 〉C （rs5275） with the susceptibility to hepatocellular carcinoma （HCC）. METHODS： A hospital-based case-control study was conducted in 780 newly and histopathologically diagnosed cases with HCC and 780 cancer-free controls frequency-matched for age, sex, nationality and residence. Genotypes of COX-2 were detected using applied biosystems TaqMan genotyping platform. Unconditional Logistic regression model and X^2 test were used to evaluate the different genotypes distribution and associations with HCC risk, respectively. RESULTS： The variant genotypes of both COX-2 -1195G〉A （adjusted OR=1. 32, 95%CI：0.94- 1.85） and 8473T〉C （adjusted OR=0.87, 95%CI：0.64-1.18） polymorphisms were not significantly associated with the risk of HCC. However, the stratified analysis revealed that under a dominant model the --1195GA＋ AA genotypes increased the risk of HCC among the youngers （less than 55 years old, adjusted OR= 1. 56, 95%CI：1. 03-2. 37）, 8473T〉C TC＋CC genotypes decreased the risk of HCC among females （adjusted OR=0. 50, 95MCI：0.25-0. 99）. The interactions between --1195G〉A polymorphisms and age, 8473T〉C polymorphisms and sex might modify the risk of HCC （P = 0. 002, P = 0. 007）. CONCLUSIONS： COX-2 -1195G〉 A and 8473T〉 C polymorphisms do not have the independent effects for the susceptibility to HCC, but the interactions between genetic polymorphisms of -1195G〉A and age, 8473T〉C and sex may modify the risk of HCC.