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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Taq Man MGB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χ2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 investigate the relationship between genetic polymorphisms of COX-2 gene-1195G> A (rs689466) and 8473T> C (rs5275) in Guangxi and the genetic susceptibility to hepatocellular carcinoma (HCC). Methods: A hospital-based case-control study was used. The study population consisted of 780 HCC patients diagnosed histologically and 780 non-tumor patients matched in age, gender and ethnicity in the same area. The genotypes of COX-2 gene were detected by Taq Man MGB probe allelic genotyping. The frequency distribution of genotypes at each locus was analyzed byχ2 test and non-conditional logistic regression model And its relationship with the risk of HCC, and to further explore the impact of gene-environment interaction on the risk of HCC. Results: The SNP-1195G> A: OR = 1.32, 95% CI: 0.94 ~ 1.85; SNP8473T> C: corrected OR = 0.87, 95% CI: 0.64-1.18). Hierarchical analysis showed that the GA + AA genotype of COX-2 gene-1195G> A increased the risk of HCC in patients under 55 years of age (adjusted OR = 1.56, 95% CI: 1.03-2.37) The 8473T> C locus TC + CC genotype reduced the risk of HCC in women (adjusted OR = 0.50, 95% CI: 0.25-0.99). Further interaction analysis showed that there was interaction between -1195G> A locus and age, 8473T> C locus of COX-2 gene and sex respectively (P = 0.002; P = 0.007). CONCLUSION: The single effect of COX-2 SNP at -1195G> A or 8473T> C may not be related to the susceptibility to HCC. However, the interaction between -1195G> A and age, 8473T> C locus and sex, Risk of illness.