Genetic susceptibility of VEGF and CCND1 to Taiwan OSCC patients

Objectives: Angiogenesis is recognized as an important risk factor in tumor progression. VEGF and Cyclin D1 (CCND1) play important roles in the angiogenesis. The polymorphisms of VEGF -634 G>C, -460 C>T , and +936 C>T, and CCND1 +870 A>G are most discussed. However, the association between VEGF and CCND1 polymorphisms and oral squamous cell carcinoma (OSCC) remain unclear. Our aims were to investigate the risks of VEGF and CCND1 polymorphisms in the malignant potential of oral precancerous lesions (OPL) and OSCC development.

Methods: A total of 324 OSCC, 53 oral leukoplakia (OL), and 67 oral submucosal fibrosis (OSF) patients, and 331 healthy controls were recruited in the present study. The polymorphisms of VEGF -634 G>C , -460 C>T , +936 C>T, and CCND1 +870 A>G were determined by PCR-RFLP methods. Statistical analysis was used to analyze the association.

Results: No differences in the distributions of VEGF and CCND1 polymorphisms were found between the OSCC, OSF, and OL patients, and healthy controls. Stratification with the habits of substance usage, VEGF -460C allele was associated with OSCC development in smokers (OR=2.31, 95%CI=1.30-4.27) and drinker (OR=1.71, 95%CI=1.03-2.88). An association of VEGF GG-634 genotype and OSCC development was found in smokers (OR=2.35, 95%CI=1.24-4.82). In betel chewers, CCND1 GG870 genotype had 3.5 times to increase the susceptibility to malignant potential of OSF (OR=3.52, 95%CI=1.22-14.89). However, in non-drinkers, the risk of CCND1 GG870 genotype to malignant potential of OL, and OSCC development were decreased (OR=0.15, 95%CI=0.04-0.65; OR=0.40, 95%CI=0.17-0.85). After adjusted for the possible confounding factors, the CCND1 GG870 genotype was against to OSCC development (OR=0.52, 95%CI=0.28-0.97).

Conclusions: We suggest that an effect of interaction between VEGF and CCND1 polymorphisms and substance usage was associated with the OSCC risk. VEGF and CCND1 polymorphisms may play a different role in OSCC development than in malignant potential of OSF.