To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls.
Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.
Immunohistochemistry and FISH of TP 53 genes were applied on 26 OSCC formalin fixed paraffin embed (FFEP) blocks selected from two oral cancer referral centers in Malaysia.
Both pRB/p16(INK4A) and p53 are dysfunctional in many cancers, including the most common type of oral cancer, squamous cell carcinoma (OSCC) and other evidence is accumulating in support of the idea that senescence acts as a barrier to tumour development and/or progression.
These findings suggest that the combined variants of p53 and p73 significantly increase the risk of HPV16-associated oral cancer, especially among never-smokers.
Our findings suggest that the homozygous Arg allele of the p53 codon 72 may be associated with the development of oral cancer and be a useful marker for primary prevention and anticancer intervention.
Our major findings are: (a) methylation of 14-3-3 gene promoter is a rare event in oral cancer; (b) it is not always associated with 14-3-3 protein levels and there is no clear relationship between its methylation and p53 mutation; (c) loss of 14-3-3 sigma expression is associated with reduced CyclinD1 gene expression.
We conclude that p53 mutations are common among oral cavity cancers in this population, and stress the significance of this study since it is the first analysis of p53 mutation in oral cancer in a southern Brazilian population.
In this study, we focused on p53 mutations in specific regions, including DNA-binding surface regions, to clarify the correlation between mutations within the specific regions of p53 and clinical outcomes of patients with oral cancers.
Our previous work showed that acquisition of immortality at the dysplasia stage of oral cancer progression was consistently associated with four changes: loss of retinoic acid receptor (RAR)-beta and p16INK4A expression, p53 mutations and activation of telomerase.
Thus the interaction between HPV oncoproteins and the p53 gene polymorphism specifically, homozygous arginine at codon 72 appears to play no role in the development of either cervical or oral cancer and also it can not serve as a biomarker for early identification of cervical, oral or breast cancer.
Thus, this cell line provides an in vitro model for elucidating the mechanism involving p53 inactivation and p21(cip1/waf1) overexpression in smokeless tobacco-induced oral cancer.