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Background  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).    Methods  We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of  MMP-1  and  MMP-3 .    Results  The frequency of the  MMP-1  2G 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-1  1G/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 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.    Conclusion  Since the 2G allele is a majority of the  MMP-1  genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the  MMP-1  2G allele in the early onset OSCC.

The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma