细胞色素P450 1B1及COMT基因多态性与子宫内膜癌易感性及与mRNA表达关系的研究

ASSOCIATION OF GENE POLYMORPHISM IN CYTOCHROME P450 1B1 AND COMT,WITH THE EXPRESSION OF mRNA AND SUSCEPTIBILITY TO ENDOMETRIAL CANCER

目的探讨细胞色素P450 1B1及儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因多态性对子宫内膜癌易感性的影响及与mRNA表达的相关性。方法采用(polymerase chain reaction-restrictionfragment length polymorphism,PCR-RFLP)方法检测122例子宫内膜腺癌患者和114例对照者CYP1B1基因119位、432位密码子和COMT基因158位密码子G→A位点的多态性。对其中36例患者采用反转录-聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)方法检测外周血淋巴细胞中CYP1B1和COMT mRNA的表达。结果 CYP1B1基因119位的突变型(T/T)基因型频率在病例组(8.2%)明显高于对照组(3.5%),432位多态性在病例组与对照组比较差异无统计学意义(P>0.05)。而COMT基因多态在绝经年龄<50岁组,合并杂合型(G/A)和突变型(A/A)与野生型(G/G)比较,病例组与对照组差异有统计学意义(P<0.05,OR=0.422)。野生型(G/G)型COMT mRNA的表达量低于杂合型(G/A)与突变型(A/A)COMT mRNA的表达量,比较差异有统计学意义(P<0.05)。结论 CYP1B1基因119位多态性与子宫内膜癌的发生有潜在的相关性,COMT基因多态与子宫内膜癌的发病风险存在相关性,绝经年龄越早,携带突变等位基因A个体的发病风险减低。所有多态中只有COMT基因第158位密码子多态影响COMT mRNA的表达。

Objective To investigate the association of gene polymorphism in cytochrome P450 I B1 and catechol- O- methyhransferase （COMT） with the susceptibility to endometrial cancer. The association of mRNA expression and gene polymorphism was explored as well. Methods This population -based case- control study, including 122 endometrial cancer patients and 114 healthy controls, were tested the genetic polymorphisms of CYPIB1 and COMT genes by polymerase chain reaction -restriction fragment length polymorphism （ PCR - RFLP）. And the mRNA expression of CYP1Bland COMT were measured by reverse transcription - polymerase chain reaction （ RT - PCR） analysis in 36 endometrial cancer patients. Results CYP1 B 1 gene at codons 119 polymorphisms, homozygous genotype （ T/T ） frequency in the case group （ 8.2% ） was higher than that of the control group, while codon 432 polymorphisms was found no significant difference between control group and the case group （ P 〉 0.05 ）. In COMT genetic polymorphism, combination of heterozygous genotype （G/A） and homozygous genotype （A/A） were compared with wild genotype （G/G）, and the results showed that the distribution in the endometrial cancer patients whose menopause ages are lower than fifty years was significantly different from that in healthy controls （ P 〈 0.05, OR = 0,422 ）. The mRNA expressiotl {tt patients with COMT wild genotype （G/G） was lower than that in the patients with the heterozygous genotype （G/A） and homozygous genotype （A/A）. The difference was significant （ P ~ 0, 05 ）, Conclusion CYPl B1 gene at codons 119 polymorphisms has a potential association with endometrial cancer. At codon 158 of COMT gene polymorphism,the individual with A allele decrease the risk of endometrial cancer when menopause age was earlier. Only COMT gene polymorphism at codon 158 affected mRNA expressions