Polymorphisms of Matrix Metalloproteinases-2 and HER-2 genes and Risks of Oral Squamous cell Carcinoma in a Taiwan Population

• Main Authors: Yen-Yun Wang, 汪硯雲
• Other Authors: Ying-Chu Lin
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/53812000366855847547

碩士 === 高雄醫學大學 === 口腔衛生科學研究所碩士班 === 96 === Abstract Background: Oral cancer is one of the major causes of cancer specific mortality in Taiwan. Matirx metalloproteinases (MMPs) play an important role in cancer development and progression. MMP-2 is one of the key factors to degrade extracellular matrix and basement membrane which are the important physical barriers in preventing against expanding growth and migration of cancer cell. Single nucleotide polymorphisms (SNPs) of MMP-2 gene located at nucleotide -1306, -790, and -735 sites were frequently discussed in previous studies. Human epidermal growth factor receptor-2 (HER-2), a proto-oncogene with a chromosomal location of 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity. This protein is a member of the epidermal growth factor receptor family that controls a variety of cellular functions, including cell proliferation. Amplification and/ or overexpression of the HER-2 gene have been found to be associated with cancer development and progression. A SNP of codon 655Ile>Val in HER-2 gene was suggested to be a susceptible genetic factor for the cancer development. However, the associations between the SNPs of -1306C>T, -790T>G, and -735C>T in MMP-2 gene, HER-2 655Ile/Val polymorphisms, and oral squamous cell carcinoma (OSCC) remain unclear. Objectives: Our aim is to investigate the association between SNPs of -1306C>T, -790T>G, and -735C>T in matrix metalloproteinase-2 (MMP2), HER-2 655Ile/Val polymorphisms, and OSCC. Material and 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 and a company health examination 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 methods. JMP statistical software version 5.01 was used to analyze the association. Results: Three hundred and twenty OSCC and 63 OSF, and 90 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. MMP-2 -1306CC vs. -1306 (CT+TT) genotype was an elevated risk factor for OSCC (OR = 1.73, 95% CI = 1.41 - 2.64). Stratification with the habits of substance usage and adjusting for age, sex ethnicity, education level, and the other two habits of substance usage, MMP-2 -1306CC genotype had 3.27-fold excess risk of OSCC development in drinker. MMP2 -1306CC genotype was associated with malignant potential of OL in participants without the cigarette smoking habit (OR = 5.54, 95% CI = 1.08 - 30.84) and those with the habit of alcohol drinking (OR = 2.39, 95%CI = 1.15 - 4.87). Participants who carried MMP-2 -790 TT genotype had 1.80-fold excess risk in malignant potential of OL compared those with G allele. After adjusted with the possible confounding factors, MMP-2 -735CC genotype was associated with lower risk for malignant potential of OL (OR = 0.51, 95% CI = 0.31 - 0.82).The distributions of HER-2 genotypes showed no significant different between OSCC, OSF, OL, and health controls (p = 0.85). No association was found between HER-2 genotypes and OSCC by stratification with substance usage and multiple logistic regression. Compared with (T-1306-G-790 + T-1306-T-790) haplotypes, the C-1306-T-790 haplotype was a risk factor for OSCC (OR = 1.90; 95% CI = 1.23 - 3.23). Compared with the T-1306-T-735 haplotype, the C-1306-C-735 and C-1306-T-735 haplotypes were associated with an increased risk of OSCC (OR = 1.76, 95% CI = 1.03 - 3.02; OR = 2.03, 95% CI = 1.15 - 3.63, respectively). Conclusions: We suggest that MMP2 -1306 CC play an important role in OSCC development and the malignant of OL, but no such association was found in HER-2 codon 655 genotypes.