Matrix metalloproteinase single-nucleotide polymorphisms and haplotypes predict breast cancer progression
Matrix metalloproteinase single-nucleotide polymorphisms and haplotypes predict breast cancer progression
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DOI：
10.1158/1078-0432.ccr-07-0884
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发表时间：
2007-11-15
影响因子：
11.5
通讯作者：
Jones, J. Louise
中科院分区：
文献类型：
--
作者：
Hughes, Simon;Agbaje, Olorunsola;Jones, J. Louise
目的：多态性。几种基质金属蛋白酶（MMP）基因的启动子区与转录水平的改变有关。我们假设个体的MMP基因型和单体型将影响乳腺肿瘤的进展并有助于预测预后。实验设计：本研究评估了128例淋巴结阴性和93例淋巴结阳性乳腺癌患者中MMP-1、MMP-3、MMP-7、MMP-9、MMP-12和MMP-13启动子区的单核苷酸多态性（SNP）与乳腺癌转移扩散的关系。研究队列为混合种族，白人患者占65%。Logistic回归分析基因型与淋巴结转移的关系，Kaplan-Meier法和log-rank检验分析基因型与总生存期的关系。单倍型和淋巴结状态之间的关联也进行了研究。结果如下：数据显示MMP-9的C/T基因型[混合种族优势比3.6，95%置信区间（95% CI）1.2-11.1;白人优势比9.1，95% CI 1.7-48.4]与MMP-1的2G/2G基因型显著且独立相关（混合种族优势比3.9，95% CI 1.7-9.4;高加索人比值比2.6，95% CI 1.0-6.9），淋巴结阳性疾病，MMP-1 2G/2G与生存率降低相关（风险比3.1，95% CI 1.1-8.7），尽管这取决于淋巴结状态。MMP-12 G等位基因驱动的两种单倍型与淋巴结阳性疾病和生存率显著相关。结论：这些结果表明，MMP单核苷酸多态性影响乳腺癌的行为，MMP-12 G/2G基因型增加淋巴结转移的风险，并预测预后不良，
Purpose: Polymorphisms within the. promoter region of several matrix metalloproteinase (MMP) genes have been linked to alterations in the level of transcription. We hypothesized that an individual's MMP genotype and haplotype will influence breast tumor progression and help predict prognosis. Experimental Design: This study has evaluated the association between single-nucleoticle polymorphisms (SNP) in the promoter regions of MMP-1 MMP-3, MMP-7 MMP-9, MMP-12, and MMP-13 and metastatic spread of breast cancer in 128 lymph node-negative and 93 lymph node-positive patients. The study cohort was of mixed ethnicity, with Caucasian patients comprising 65%. Associations between genotype and lymph node status were estimated by logistic regression and with overall survival using the method of Kaplan-Meier and log-rank test. Associations between haplotype and lymph node status were also investigated. Results: The data show a significant and independent association of the C/T genotype for MMP-9 [mixed ethnicities odds ratio 3.6, 95% confidence interval (95% CI) 1.2-11.1; Caucasian odds ratio 9.1, 95% CI 1.7-48.4] and the 2G/2G genotype for MMP-1 (mixed ethnicities odds ratio 3.9, 95% CI 1.7-9.4; Caucasian odds ratio 2.6, 95% CI 1.0-6.9) with lymph node-positive disease, MMP-1 2G/2G was associated with reduced survival (hazard ratio 3.1, 95% CI 1.1-8.7), although this is dependent on lymph node status. Two haplotypes, driven by the MMP-12G allele, were significantly associated with lymph node-positive disease and survival. Conclusions: These results suggest that MMP single-nucleoticle polymorphisms influence breast cancer behavior and that the MMP-12G/2G genotype increases the risk of lymph node metastasis and predicts poor prognosis,