A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility.
OBJECTIVE
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.


METHODS
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.
Ghilardi
Giorgio
G
Dipartimento di Medicina Chirurgia e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano, Polo S. Paolo, I-20142 Milan, Italy. giorgio.ghilardi@unimi.it
Biondi
Maria Luisa
ML
Caputo
Maria
M
Leviti
Simona
S
DeMonti
Marco
M
Guagnellini
Emma
E
Scorza
Roberto
R
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1