Impact of uPA System Gene Polymorphisms on the Susceptibility of Environmental Factors to Carcinogenesis and the Development of Clinicopathology of Oral Cancer
- 178 Downloads
The levels of urokinase plasminogen activator (uPA) system in tumor tissues are implicated as prognostic biomarkers in a wide range of malignancies. However, their possible impact on the risk and prognosis of oral cancer and the susceptibility of environmental carcinogens to oral cancer remains poorly investigated.
The genetic polymorphisms of uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 253 patients with oral cancer and 344 healthy controls.
There was no significant effect of uPA system genes on the susceptibility of oral cancer; however, the impact of uPA system gene polymorphisms on the susceptibility of betel nut and tobacco consumptions to oral cancer was revealed, except for that of uPAR gene polymorphism on tobacco consumption. Patients with oral cancer with at least one 5G allele of PAI-1 gene have a low risk for the development of clinical stage III or IV (p ≤ 0.05) and lymph node metastasis (p ≤ 0.05) compared with those with 4G/4G homozygotes.
Our results suggest that the combination of uPA system gene polymorphisms and environmental carcinogens was related to the risk of oral cancer, and the genetic polymorphism of PAI-1 was associated with a low risk to the clinicopathological development of oral cancer.
KeywordsOral Cancer Oral Squamous Cell Carcinoma Oral Squamous Cell Carcinoma Tobacco Consumption Environmental Carcinogen
This study was supported by a research grant from National Science Council, Taiwan (NSC98-2314-B-317-003-MY3). PCR was performed in the Instrument Center of Chung Shan Medical University, which is supported by National Science Council, Ministry of Education and Chung Shan Medical University.
- 19.de Haas EC, Zwart N, Meijer C. Association of PAI-1 gene polymorphism with survival and chemotherapy-related vascular toxicity in testicular cancer. Cancer. 2010 (in press).Google Scholar
- 35.Nielsen HJ, Pappot H, Christensen IJ, et al. Association between plasma concentrations of plasminogen activator inhibitor-1 and survival in patients with colorectal cancer. Br Med J. 1998;316:829–30.Google Scholar
- 43.Hundsdorfer B, Zeilhofer HF, Bock KP, et al. Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal neoplastic tissues of patients with squamous cell cancer of the oral cavity: clinical relevance and prognostic value. Craniomaxillofac Surg. 2005;33:191–6.Google Scholar
- 46.Czekay RP, Loskutoff DJ. Unexpected role of plasminogen activator 1 in cell adhesion and detachment. Exp Biol Med. 2004;229:1090–6.Google Scholar