基质金属蛋白酶3基因启动子的5A/6A多态性与乳腺癌

The 5A/6A polymorphism of the matrix metalloproteinase 3 gene promoter and breast cancer.

作者信息

Krippl Peter, Langsenlehner Uwe, Renner Wilfried, Yazdani-Biuki Babak, Köppel Herwig, Leithner Andreas, Wascher Thomas C, Paulweber Bernhard, Samonigg Hellmut

机构信息

Department of Internal Medicine, Division of Oncology, Medical University Graz, Graz, Austria.

出版信息

Clin Cancer Res. 2004 May 15;10(10):3518-20. doi: 10.1158/1078-0432.CCR-04-0010.

DOI:10.1158/1078-0432.CCR-04-0010

PMID:15161710

Abstract

PURPOSE

The matrix metalloproteinase 3 (MMP3), also known as stromelysin-I, is a key-player for carcinogenesis and tumor growth. A 5A/6A promoter polymorphism is associated with differences in MMP3 activity and has been linked to cancer susceptibility in some studies. In the present study we evaluated the role of this polymorphism for breast cancer risk.

EXPERIMENTAL DESIGN

A case-control study was performed including 500 patients with histologically confirmed breast cancer and 500 female, age-matched, healthy control subjects from population-based screening studies. The MMP3 5A/6A polymorphism was determined by a 5'-nuclease (TaqMan) assay.

RESULTS

Prevalences of 5A/5A, 5A/6A, and 6A/6A genotypes were similar among patients (20.6, 51.8, and 27.6%, respectively) and controls (23.3, 47.3, and 29.4%, P = 0.34). The odds ratio of carriers of a MMP3 5A allele for breast cancer was 1.09 (95% confidence interval, 0.83-1.44). Patients with the 5A/5A genotype had a higher proportion of lymph-node metastases than those with a 5A/6A or 6A/6A genotype (P = 0.010).

CONCLUSIONS

The MMP3 5A/6A promoter polymorphism does not appear to influence breast cancer susceptibility but may be linked to a higher risk for metastasizing among breast cancer patients.

摘要

目的

基质金属蛋白酶3（MMP3），也称为基质溶解素-1，是致癌作用和肿瘤生长的关键因子。一种5A/6A启动子多态性与MMP3活性差异相关，并且在一些研究中已与癌症易感性相关联。在本研究中，我们评估了这种多态性对乳腺癌风险的作用。

实验设计

进行了一项病例对照研究，包括500例经组织学确诊的乳腺癌患者和500名来自基于人群的筛查研究的年龄匹配的女性健康对照者。通过5'-核酸酶（TaqMan）分析确定MMP3 5A/6A多态性。

结果

5A/5A、5A/6A和6A/6A基因型的患病率在患者（分别为20.6%、51.8%和27.6%）和对照者（分别为23.3%、47.3%和29.4%，P = 0.34）中相似。MMP3 5A等位基因携带者患乳腺癌的比值比为1.09（95%置信区间，0.83-1.44）。5A/5A基因型的患者发生淋巴结转移的比例高于5A/6A或6A/6A基因型的患者（P = 0.010）。