2G allile of MMP-1 gene polymorphism increases risk of oral cancer

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Matrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC). We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3. The frequency of the MMP-12G allele was higher and that of the 1G homozygote was lower in the OSCC cases (p=0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47 fold) risk of OSCC (95%CI 1.47-4.14, p=0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95%CI 1.15-4.58, p=0.018), indicating independent involvement of these factors, in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-11G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 84.4% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue. Since the 2G allele is a majority of the MMP-1 genotype in the general population, the effect of MMP-12G allele was thought to act as a genetic background However this report provides evidence for the critical impact of the MMP-12G allele in the early onset OSCC.