Association of -1171 Promoter Polymorphism of Matrix Metalloproteinase-3 with Increased Risk for Oral Cancer

Abstract

Background: Matrix metalloproteinase-3 (MMP-3) plays a pivotal role in inflammation and thrombosis. Increased levels of MMP-3 have been correlated with progression of oncogenesis and metastasis. Inflammation-related factors have recently been found to contribute to the development of malignancies. The present study investigated the possible association of -1171 5A/6A polymorphism, which influences expression of MMP-3, with risk for oral cancer. Materials and Methods: This polymorphism was examined by restriction enzyme analysis in 160 patients with oral squamous cell carcinoma (OSCC) and 156 healthy controls of equivalent gender, age and ethnicity (Greeks and Germans). Results: A significant increase of 5A/6A heterozygotes was observed in the whole group and several subgroups of patients compared to controls (p<0.05). Nevertheless, in these subgroups and the whole patient group, the 5A allele and carrier frequencies did not differ significantly from those of the control group. The only significant increase of 5A allele-related frequencies (p<0.05) in comparison with controls was observed in subgroups of patients with a positive family history of cancer (5A allele carrier frequency only), with advanced stages of cancer (5A allele frequency only) and without positive history of thrombophilia (both 5A allele and carrier frequencies). In addition, the genotypes containing the 5A allele (5A/5A and 5A/6A) had a double risk of OSSC development in smokers (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.04-4.48 and OR 1.78, 95% CI 1.01-3.13, respectively). Conclusion: The results of this study suggest that the high expression 5A allele of the MMP-3 gene is associated with an increased risk for oral cancer in certain individuals.