A Metalloproteinase-9 Polymorphism Which Affects Its Expression is Associated with Increased Risk for Oral Squamous Cell Carcinoma

Aim: In light to recently found contribution of factors associated with angiogenesis, thrombosis and inflammation to carcinogenesis, we investigated the possible association of metalloproteinase-9 (MMP-9) with increased risk of oral cancer.

Methods: In DNA samples of 152 patients with oral squamous cell carcinoma and 162 healthy controls of comparable ethnicity, age and sex, we studied the -1562 C/T polymorphism in the MMP-9 gene promoter, which affects its transcription.

Results: The detected frequency for the high expression T allele in the patients' group was significantly increased in comparison to that of the control group (22% versus 15%, respectively; P<0.05). This difference was due to the relative increase of C/T heterozygotes in the group of patients, in comparison to controls (P<0.05, 95% OR 1.92, CI 1.21-3.06). The same pattern of significance was observed between controls and the subgroups of patients with initial (I & II) stages of cancer, without positive family history of cancer or thrombophilia, with smoking and alcohol abuse habits.

Conclusions: The investigated MMP-9 polymorphism has a strong association with increased risk for developing oral cancer in a subset of the general population. These results are in accordance to previous studies of constitutive expression and secretion of MMP-9 in invasive oral carcinoma cell lines. The observation that T allele carriers have an increased risk for developing oral cancer only in initial stages, but not in advanced ones, may be due to the role of MMP-9 in the inhibition of angiogenesis by generating angiostatin from plasminogen.