title: Polymorphisms and Plasma Levels of Tissue Inhibitor of Metalloproteinase-3: Impact on Genetic Susceptibility and Clinical Outcome of Oral Cancer.
abstract: Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants-1200 healthy male controls and 747 male patients with oral cancer-were recruited. Allelic discrimination of TIMP3 -1296 T > C (rs9619311), TIMP3 C > T (rs9862), and TIMP3 C > T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2-2.1] after adjustment for betel quid chewing, alcohol, and tobacco consumption. Among 601 betel quid chewers, the TIMP3 polymorphism rs9862 T/T carriers had a 32.2-fold (95% CI, 20.2-51.3) increased oral cancer risk compared with those carrying C/C and not chewing betel quid. In addition, the authors observed a significant association between rs9862 variants and large tumors (OR, 1.5; 95% CI, 1.0-2.3) development. Moreover, TIMP3 plasma levels significantly increased in oral cancer patients who have large tumor or carry T allele rs9862 polymorphism. In conclusion, these results suggest that gene-environment interactions between the TIMP3 rs9862 polymorphisms and betel quid may alter oral cancer susceptibility and tumor growth in Taiwanese men.
authors.affiliation: From the Institute of Medicine, Chung Shan Medical University, Taichung (C-WS, Y-WH, M-KC, S-FY); Department of Health, Pulmonary and Critical Care Unit, Chang Hua Hospital (Y-WH); Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua (M-KC); Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan (S-CS), Department of Medical Research, Chung Shan Medical University Hospital (S-FY), Department of Dentistry, Chung Shan Medical University Hospital (C-WL), and Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan (C-WL).
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Su
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013624:Taiwan; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000097:blood / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3