Matrix metalloproteinase-1 promoter polymorphism 1G/2G is correlated with colorectal cancer invasiveness.
OBJECTIVE
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).


METHODS
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.
Ghilardi
G
G
Dipartimento di Medicina, Chirurgia e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano-Polo S. Paolo, Via A. Di Rudini, I-20142 Milan, Italy. giorgio.ghilardi@unimi.it
Biondi
M L
ML
Mangoni
J
J
Leviti
S
S
DeMonti
M
M
Guagnellini
E
E
Scorza
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
D004247:DNA; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1