Abstract P4-07-09: The Impact of Matrix Metalloproteinase-1 Promoter 1G/2G Polymorphism on Breast Diseases
| Autor: | Jeffrey A. Hooke, Stella Somiari, Jennifer Kane, J Zhou, Brenda Deyarmin, Richard J. Mural, Constance E. Brinckerhoff, J Saini, Craig D. Shriver, Susan M. Lubert |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:P4-07 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.sabcs10-p4-07-09 |
| Popis: | Background: Matrix Metalloproteinase-1 (MMP-1) is a ubiquitously expressed interstitial collagenase. Overexpression of MMP-1 has a role in initiating mammary tumorigenesis by degrading stroma and by releasing growth factors. A single guanine insertion polymorphism in the MMP-1 promoter creates the binding site, 5'-GGAA-3', for the Ets transcription factor, and increases transcription of MMP-1. The MMP-1 2G polymorphism is linked to early onset, increased risk or aggressiveness of several cancers. Its relationship with other potential markers in invasion and metastasis of breast cancer is unknown. Experimental Design: To study the impact of the 2G polymorphism on breast cancer we analyzed the genotypes of 109 patients (52 invasive breast cancer [IBC], 29 ductal carcinoma in situ [DCIS], 13 atypical ductal hyperplasia [ADH] and 15 benign breast disease). Immunohistochemical (IHC) data for MMP-1, HER2, ER/PR and P53 from these donors were also analyzed. IHC results for MMP-1 were scored as 0 (no expression) or increasing expression of+1, +2 or +3. Data were analyzed using Pearson's chi-square test to identify statistical significance. Results: A significantly higher number of patients in the IBC group expressed high MMP-1 (+2 and +3; p Conclusions: 1) In the IBC group, the 2G insertion polymorphism contributes to MMP-1 over expression. 2) Increased expression of MMP-1 in ADH and higher 2G allele frequency are consistent with the hypothesis that increased MMP-1 2G polymorphism plays a role in initiation of ADH through up regulation of MMP-1 expression. 3) Earlier studies show prognostic role for the coexistence of increased expression of HER2 and P53 in breast cancer. Our observation of a significant increase in the 2G homozygotes in HER2 and P53 positive patients supports a prognostic role for this polymorphism and suggests its possible association with other breast cancer markers. Thus, the MMP-1 2G polymorphism may both contribute to breast disease onset and serve as a prognostic marker for breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-09. |
| Databáze: | OpenAIRE |
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