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Matrix Metalloproteinase-1 Promoter Polymorphism 1G/2G Is Correlated with Colorectal Cancer Invasiveness

Dipartimento di Medicina, Chirurgia e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano-Polo S. Paolo [G. G., J. M., M. D., R. S.], and Laboratorio di Chimica Clinica e Microbiologia, Ospedale S. Paolo-Polo Universitario [M. L. B., S. L., E. G.], I-20142 Milano, Italy

Purpose: Matrix metalloproteinase-1 (MMP-1) is likely to be involved in invasion and metastasis of several tumors by degrading the extracellular matrix. A single guanine insertion polymorphism (2G) in the MMP-1 promoter region creates an Ets binding site causing the elevation of transcriptional level and local expression of MMP-1. The aim of this study was to evaluate the impact of this 2G insertion type polymorphism on invasion and metastasis of colorectal cancer (CRC).

Experimental Design: We genotyped for this 1G/2G polymorphism 60 patients, who were operated on for CRC and followed for 6–30 months (median: 21). A control population of 164 age- and sex-matched tumor-free subjects was also genotyped for the same polymorphism.

Results: The proportion of 2G homozygotes was higher in the CRC group than in the controls (P = 0.014; odds ratio, 2.21; 95% confidence interval, 1.17–4.16). The CRC group was divided in a group without metastasis (M-) and a group that had developed metastasis (M+). At the time of diagnosis, 2G homozygotes were more represented in the M+ group than in M- (P = 0.0082; odds ratio, 4.73; 95% confidence interval, 1.46–15.26). The difference between M- patients and controls did not achieve statistical significance (P = 0.52).

Conclusions: Our results suggest that the presence of 2G polymorphism at the MMP-1 promoter region may favor the growth and the metastatic process in CRC patients and could be looked at as a risk factor for a worse prognosis.

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