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AIM Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. MATERIALS AND METHODS In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. RESULTS The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). CONCLUSION The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

BACKGROUND/AIM Matrix metalloproteinases (MMPs) control the homeostasis of the extracellular matrix and their genetic polymorphisms may contribute to cancer susceptibility. The aim of this study was to reveal the genotypes of MMP8 among the Taiwanese and examine the contribution of MMP8 C-799T, Val436Ala and Lys460Thr polymorphisms to bladder cancer. MATERIALS AND METHODS MMP8 C-799T, Val436Ala and Lys460Thr polymorphic genotypes were determined in 375 patients with bladder cancer and 375 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS Regarding MMP8 C-799T, there was no significant differential distribution between patient and control groups [p for trend=0.6629]. The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at MMP8 C-799T were 1.13 (95%CI=0.89-1.44, p=0.3688) and 1.10 (95%CI=0.87-1.52, p=0.9030), respectively, compared to those carrying the wild-type CC genotype. Regarding MMP8 Val436Ala, there was no significant differential distribution between patient and control groups [p for trend=0.8166]. The adjusted OR for those carrying AC and CC genotypes at MMP8 Val436Ala were 0.71 (95%CI=0.31-2.28, p=0.6094) and 1.00 (95%CI=0.21-4.73, p=0.7247), respectively. The polymorphism Lys460Thr at MMP8 was not found among Taiwanese patients. CONCLUSION MMP8 C-799T, Val436Ala and Lys460Thr may only play an indirect role in determining personal cancer susceptibility for bladder cancer in Taiwan.