环氧化酶-2基因-1195G>A和-765G>C多态性与膀胱癌发病风险的关系

Correlation study between nucleotide polymorphisms of cyclooxygenase-2 gene and bladder cancer risk

目的环氧化酶-2基因（COX-2）的表达水平与临床病理特征有相关性,多态性可影响其表达水平,本文探讨COX-2的两个功能性单核甘酸多态（single nucleotide polymorphisms,SNPs）与膀胱癌易感性的关系。方法研究对象为250例经组织学确诊的膀胱癌病例和275例相匹配的无肿瘤史的正常人群。采用聚合酶链反应-限性片段长度多态性方法（PCR-RFCP）测COX-2基因-1195G/A和-765G〉C多态的基因型,比较不同基因型与膀胱癌的关系,并分析其与分期、分级、吸烟之间的关系。结果 COX-2基因1195GG、GA和AA基因型在病例组和对照组间的频率分布有统计学意义（P〈0.05）,变量Logistic回归分析显示-1195AA基因型与膀胱癌发生的风险升高相关,OR值分别为（SNP-1195 GA＋AA：OR=2.15,95%CI=1.25--3.70）,含有A等位基因的GA＋AA基因型相对于GG基因型,患者年龄、肿瘤分化程度、TNM分期及吸烟差异有统计学意义（P〈0.05）。结论 COX-2基因启动子区的-1195G〉A单核苷酸多态与可能膀胱癌遗传易感性相关,且可能与膀胱癌的肿瘤分化和TNM分期有关。

Objective To explore the correlation of two functional nucleotide polymorphisms（-1195G/A,-765G 〉 C） in the cyclooxygenase-2（COX-2） gene with the genetic susceptibility on bladder cancer risk in a Chinese population of Nan- jing city. Methods Total of 250 bladder cancer and 275 control people peripheral blood samples were collected and the COX-2 genotype was analyzed by polymerase chain reaction -restricted fragments length polymorphism（ PCR-RF LP）. Re- suits There was statistical difference only in the genotype frequency of -l195G/A between the cases and controls. Logis- tic regression analysis showed that the variant genotype of COX-2 -l195G/A polymorphism was significantly associated with susceptibility to bladder cancer（ OR = 2.15,95% CI = 1.25-3.70）. Subjects who carried at least one A allele（ AA or GA） was correlated with elder age, poor differentiation, higher TNM and greater smoking compared with GG genotype （ P 〈 0.05 ）. Conclusion The SNP of-1195A 〉 G in the COX-2 promoter may play an important role in mediating sus- ceptibility to developing bladder cancer and also related with cancer differentiation and progression.