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.