COMT基因多态性与乳腺癌发生及发展相关性探讨

目的：探讨与雌激素灭活相关的基因儿茶酚-O-甲基转移酶（COMT）基因多态性与乳腺癌发生及发展的关系。方法：采用聚合酶链反应-限制性片段长度多态性分析技术，对200例乳腺癌及100例正常乳腺组织的COMT基因第4外显子第158密码子G／A（Val／Met）多态性进行分析，采用免疫组织化学法检测乳腺癌组织ER、PR、p53及c—erbB-2蛋白的表达。比较各组中各种基因型分布频率的差异．以及各种基因型与乳腺癌预后相关因素间的关系。结果：乳腺癌患者COMT纯和变异基因型发生率显著高于对照组（P=0．0267）。随着乳腺癌，临床分期（P=0．0082）、组织学分级（P=0．0146）的升高及淋巴结转移数目的增加（P=0．0387），变异性基因型所占比例明显增大、在肿瘤组织ER阳性的患者中，COMT基因型与，临床分期（P=0．0004）、组织学分级（P=0．0116）及淋巴结转移（P=0．0008）间关系的差异更加显著、结论：Met／Met变异基因型与乳腺癌危险性相关；具有低活性COMT等位基因（COMT—LL及COMT—HL）的乳腺癌患者与高临床分期、高组织学分级以及淋巴结转移多等预后不良的因素相关。

The Relationship between Catechol-O-Methyltransferase (COMT) Polymorphisms and the Development of Breast Cancer

Objective: To investigate the relationship between COMT genetic polymorphisms and the development and prognosis of breast cancer. Methods: A G/A (Val/Met) polymorphism in codon 158 in exon 4 of COMT was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 cases with breast cancer and 100 samples of normal breast tissue. The expression of ER, PR, p53 and CerbB-2 was detected in the samples using immunohistochemistry. The difference in genotypic distribution frequency between the groups, the correlation between the genotypes and the factors related to prognosis were analyzed. Results: The incidence of homozygous and variant genotypes in breast cancer was significantly higher than in the controls (P=0.026 7). The proportion of variant genotype increased as clinical stage (P=0.0082) and histological grades (P=0.014 6) advanced, as well as with increased numbers of lymph node metastases (P=0.038 7). In the ER positive group, there was a more significant correlation between the COMT genotypes and the clinical stage (P=0.000 4), histological stages (P=0.011 6) and lymph node metastasis (P=0.000 8). Conclusion: The variant genotype (Met/Met) is associated with breast cancer risk. In patients with breast cancer there is a correlation between the low activity COMT allele (COMT-LL and COMT-HL) and some factors indicating poor prognosis, including more lymph node metastases as well as a more advanced clinical stage and histological grouping.