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Molecular Oncology, Markers, Clinical Correlates |
Dipartimento di Medicina Chirurgia e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano, Polo S. Paolo, I-20142 Milan, Italy [G. G., M. C., M. D., R. S.], and Laboratorio di Chimica Clinica e Microbiologia, Ospedale S. Paolo, Polo Universitario, I-20142 Milan, Italy [M. L. B., S. L., E. G.]
Purpose: Matrix metalloproteinases (MMPs) are likely to be involved in invasion and metastasis of several tumors by degrading the extracellular matrix. A single adenine insertion/deletion polymorphism (5A/6A) in the MMP-3 promoter region causes the elevation of transcriptional level and local expression of MMP-3. The aim of this pilot study was to evaluate the impact of this 5A/6A polymorphism on susceptibility and metastasis in breast cancer.
Experimental Design: Genotyping for 5A/6A polymorphism was performed in 86 Italian women operated on for breast cancer and followed for 6–30 months (median follow-up, 21 months). A control population of 110 Italian age-matched tumor-free women was also genotyped for the same polymorphism. The 1G/2G gene promoter polymorphism for MMP-1 was additionally tested.
Results: The frequency of 5A allele was higher in the breast cancer group than in controls (P = 0.035; odds ratio, 1.53; 95% confidence interval, 1.02–2.29). The breast cancer group was divided into a group without metastasis (M-) and a group that had developed metastasis (M+). At the time of diagnosis, the 5A allele was more prevalent in the M+ group than in controls (P = 0.010; odds ratio, 1.96; 95% confidence interval, 1.16–3.30). The difference between M- patients and controls did not reach statistical significance (P = 0.37). This study was not able to demonstrate any statistical differences with respect to 1G/2G polymorphism between controls and cases and between M+ and M- subgroups.
Conclusions: Although this should be considered only as a pilot study, our results suggest that the presence of 5A polymorphism at the MMP-3 promoter region may represent an unfavorable prognostic feature in breast cancer patients associated with more invasive disease.
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