The Association Between Polymorphisms of VEGF and Cyclin D1 and Oral Squamous Cell Carcinoma in a Taiwan Population

Autor: Chia-Wen Lee, 李佳玟
Rok vydání: 2008
Druh dokumentu: 學位論文 ; thesis
Popis: 96
Background: Vascular endothelial growth factor (VEGF) has been considered to be a critical angiogenic cytokine involved in the development of several tumors. The dysfunction in the control of cell cycle accelerates the tumor development. The cyclin D1 gene was involved in the G1-S checkpoint of cell cycle. However, the association between polymorphisms of VEGF and cyclin D1 genes and oral squamous cell carcinoma remain unclear. Study objective: Our aims were to investigate the risks of VEGF -460C>T, +405C>G, and +936C>T polymorphisms and Cyclin D1 +870A>G polymorphisms to OSCC. Methods: A total of 324 oral squamous cell carcinoma (OSCC), 64 oral submucosal fibrosis (OSF) and 83 oral leukoplakia (OL) patients were recruited from the department of Oral and Maxillofacial Surgery, Kaohsiung Medical University Hospital. A total of 331 participants were recruited from a community health survey and a company health examination in the southern Taiwan. After participants signed the informed consent, we collected 10ml of peripheral blood for DNA isolation. A standardized questionnaire was applied to collect the information about substance usage and demographic data. The polymorphisms of VEGF -460C>T, +405C>G, and +936 C>T, and Cyclin D1 +870A>G were determined by PCR-RFLP methods. The JMP 5.01 statistical software was used to analyze the association. Results: After adjusting with age, gender, ethnicity, educational levels, smoking, drinking and betel quid chewing, an association of the cyclin D1 +870CC genotype with lower risk of OSCC (OR adjusted = 0.48, 95% CI = 0.23 - 0.98), particularly in non-chewers (ORadjusted = 0.30，95% CI = 0.07 - 0.98) and in non-drinkers (ORadjusted = 0.14，95% CI = 0.03 - 0.49). No association was found between VEGF -460C>T, +405C>G, and +936C>T polymorphisms and OSCC, OSF or OL. Stratification with the habits of substance usage or not, VEGF -460(CT+CC) genotype was associated with OSCC development in smokers (OR adjusted = 2.11, 95% CI = 1.05 - 4.43). Cyclin D1 +870GG genotype was a risk factor for malignant potential of OL in drinkers (OR adjusted = 2.20，95% CI = 1.03 - 4.98); however an association of the cyclin D1 +870CC genotype with lower risk for malignant potential of OL in non-drinkers (OR adjusted = 0.15，95% CI = 0.02 - 0.87). Further to analyze the risks of the VEGF -460C>T, +405C>G, and +936C>T polymorphisms in the OSCC development, malignant potential of oral precancerous lesion, and development of oral precancerous lesions. We stratified the participants by the VEGF genotypes to determine the association between the habits of three substances’ usage and oral lesions. The association between the habits of three substances’ usage and oral lesions could be differentiated by the different VEGF genotypes. Conclusion: We suggest that an effect of the interaction between the habits of betel quid chewing and alcohol drinking, and Cyclin D1 +870A>G polymorphisms on OSCC development. The association of Cyclin D1 +870A>G polymorphisms with malignant potential of OL was affected by the habit of alcohol consumption. The association between the habits of three substances’ usage and malignant potential of OSF, OSCC development, OSF development, OL development were differentiated by the VEGF -460C>T, +405C>G, and +936C>T polymorphisms.
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