Genetic susceptibility of MMP-2 and Her-2/neu to OSCC in Taiwan

Objectives: Our aim is to investigate the association between single nucleotide polymorphisms (SNP) of -1306C>T, -790T>G, and -735C>T in matrix metalloproteinase-2 (MMP2), the 655Ile/Val SNPs in human epidermal growth factor receptor-2 (HER-2 ), and oral squamous cell carcinoma (OSCC).

Methods: Patients with oral submucosal fibrosis (OSF), oral leukoplakia (OL), and OSCC were recruited from Kaohsiung Medical University Hospital. Healthy controls were recruited from a community health survey in Southern Taiwan. After inform consent, peripheral blood was collected for DNA extraction and a standardized questionnaire was applied to collect demographic data, and potential confounding factors. Genetic polymorphisms were determined using PCR-RFLP and DHPLC. JMP statistical software was used to analyze the association.

Results: Three hundred and twenty OSCC and 52 OSF, and 74 OL patients and 338 health controls were recruited into this study. OSCC, OSF, and OL patients had higher frequencies in the habits of substance usage than health controls. OSCC patients had higher frequencies of MMP2 -790T/T (OR= 1.76, 95%CI = 1.01 – 3.02) and -1306C/C (OR= 2.13, 95%CI = 1.12-3.92) genotypes than OL patients. Stratification with the habits of substance usage, MMP2 -1306C/C were associated with malignant potential of OL in participant with the betel guid chewers (OR= 2.14, 95%CI= 1.08-4.10) and alcohol drinking (OR=2.98, 95%CI=1.44-6.05). The distributions of HER-2 genotypes showed no significant different between OSCC, OSF, OL, and health controls (p = 0.85). After stratification with substance usage, no association was found between HER-2 genotypes and OSCC. After adjusted for the possible confounding factors, MMP2 -735C/C (OR= 1.73, 95% CI =1.05-2.89) and MMP2 -1306C/C (OR=1.91, 95% CI = 1.00-3.69) was risk factor for OSCC development.

Conclusions: Our findings suggest that MMP2 -1306 C/C play an important role in the malignant of OL and OSCC, but no such association was found in HER-2 codon 655 genotypes.