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Background: The goal of our study was to evaluate the influence of genetic polymorphisms of matrix metalloproteinases (MMP)-2, MMP-3 and MMP-7 on susceptibility to endometrial cancer. Methods: In the present study, we enrolled a total of 118 patients with endometrial cancer confirmed by histopathology, and 229 unrelated healthy individuals. Polymorphism for the MMP-2 (rs2285053), MMP-3 (rs3025058) and MMP-7 (rs11568818) genes was genotyped by polymerase chain reaction-restriction enzyme length polymorphism. Results: The frequencies of MMP-7 −181 G/G and A/G genotypes were found to be significantly higher in cancer patients compared with healthy controls (p=0.017). Stratification showed that individuals with MMP-7 −181 G allele were at increased risk for endometrial cancer when >50 years of age [odds ratios (OR)=2.03; 95% confidence interval (CI) 1.21–3.39], endometrioid (OR=1.80; 95% CI 1.11–2.92), low (stage I–II) (OR=1.73; 95% CI 1.05–2.83) or high stage (stage III–IV) (OR=2.69; 95% CI 1.16–6.24). Compared with the A/A genotype, the A/G+G/G genotype modified the risk of developing endometrial carcinoma and significance was detected in patients over 50 years old, and those with endometrioid type and high stage endometrial cancer. However, no significant difference in MMP-2 (-735 C/T) and MMP-3 (6A/5A) genotypes was observed between endometrial carcinoma cases and controls. Conclusions: This is the first report on the association of MMP-2, MMP-3 and MMP-7 gene polymorphisms in endometrial cancer. Our results suggest that individuals with the MMP-7 −181 G/G and A/G genotype may have an increased risk of developing endometrial cancer. Clin Chem Lab Med 2010;48:337–44. [ABSTRACT FROM AUTHOR]