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

The 5A/6A polymorphism of the matrix metalloproteinase 3 gene promoter and breast cancer
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DOI:
10.1158/1078-0432.ccr-04-0010
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发表时间:
2004-05-15
影响因子:
11.5
通讯作者:
Samonigg, H
Samonigg, H
中科院分区:
医学1区
文献类型:
--
作者:
Krippl, P;Langsenlehner, U;Samonigg, H

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目的:基质金属蛋白酶3 (matrix metalloproteinase 3, MMP3),又称基质溶素-1,是肿瘤发生和生长的关键因子。5A/6A启动子多态性与MMP3活性差异有关,并在一些研究中与癌症易感性有关。在目前的研究中,我们评估了这种多态性在乳腺癌风险中的作用。实验设计:进行病例对照研究,包括500名组织学证实的乳腺癌患者和500名年龄匹配的健康女性对照,来自基于人群的筛查研究。采用5′-核酸酶(TaqMan)检测MMP3 5A/6A多态性。结果:患者中5A/5A、5A/6A和6A/6A基因型的患病率与对照组(分别为20.6%、51.8%和27.6%)相似(分别为23.3%、47.3%和29.4%,P = 0.34)。MMP3 5A等位基因携带者乳腺癌的优势比为1.09(95%可信区间为0.83-1.44)。5A/5A基因型患者的淋巴结转移比例高于5A/6A和6A/6A基因型患者(P = 0.010)。结论:MMP3 5A/6A启动子多态性似乎不影响乳腺癌易感性,但可能与乳腺癌患者转移风险增加有关。
Purpose: The matrix metalloproteinase 3 (MMP3), also known as stromelysin-1, 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.