PAI-1-675 4G/5G polymorphism as a prognostic biomarker in breast cancer
PAI-1-675 4G/5G polymorphism as a prognostic biomarker in breast cancer
复制标题
DOI：
10.1007/s10549-007-9635-3
复制
发表时间：
2008-05-01
影响因子：
3.8
通讯作者：
Foersti, Asta
中科院分区：
文献类型：
--
作者：
Lei, Haixin;Hemminki, Kari;Foersti, Asta
尿激酶纤溶酶原激活（uPA）系统介导的细胞外基质降解是肿瘤侵袭和转移的关键步骤。肿瘤中高水平的uPA及其抑制剂PAI-1与乳腺癌预后不良相关。我们研究了uPA系统基因的遗传变异是否影响乳腺癌的易感性和预后。我们对959名瑞典乳腺癌患者的uPA系统的6个基因中的8个潜在功能单核苷酸多态性（snp）进行了基因分型，这些患者具有详细的临床数据，并与952名匹配的对照者进行了长达15年的随访。我们使用无条件逻辑回归模型来评估基因型与乳腺癌风险和肿瘤特征之间的关系。采用Kaplan-Meier法估计生存概率；采用log-rank检验检验亚组间差异。没有一个snp会增加乳腺癌的风险，但是有几个snp与一些传统的预后因素相关。最重要的是，我们发现PAI-1基因中的-675 4G/5G SNP是一种很有希望的乳腺癌预后生物标志物。与4G/4G和4G/5G基因型相比，5G/5G纯合性与较差的生存率显著相关(RR 2.04, 95% CI 1.45-2.86， P
Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P