The Ras/RAF/MEK/ERK1/2 pathway is important in the control of growth signals, differentiation and cell survival. Over-expression and activation of this pathway have been reported in different types of cancer. This study analyses the promoter methylation and RNA expression profiles of ERK and RAF1 genes with risk of oral squamous cell carcinoma (OSCC) along with the promoter methylation status of ERK and RAF1 genes using a methylation-specific polymerase chain reaction (MS-PCR) in 86 paraffin-wax embedded samples of OSCC and 68 normal control tissues. Furthermore, ERK and RAF1 expression was analysed in 19 cases and 20 normal samples by real-time reverse transcription PCR. Frequency of promoter methylation was detected for ERK (93.02% and 6.98%) and RAF1 (95.35% and 4.65%) genes in cases and controls, respectively. Messenger RNA (mRNA) expression analysis indicated statistically significant difference between cases and controls for ERK (P < 0.002) and RAF1 (P < 0.006). The authors believe that this is the first report to show that expression of ERK and RAF1 is involved in risk of OSCC.

Background: Apoptosis is an important mechanism that is responsible for the physiological deletion of harmful, damaged, or unwanted cells. Changed expression of apoptosis-related genes may lead to abnormal cell proliferation and finally to tumorigenesis. Our aims were to analyze the promoter methylation and gene expression profiles of FADD and FAS genes in risk of OSCC. Material and Methods: we analyze the promoter methylation status of FADD and FAS genes using Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68 normal oral tissues applied as control. Also, FADD and FAS genes expression were analyzed in 19 cases and 20 normal specimens by Real-Time Reverse-Transcripts PCR. Results: Aberrant promoter methylation of FADD and FAS genes were detected in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively, with a significant difference between cases and healthy controls for both FADD and FAS genes (P<0.001). The gene expression analysis showed statistically significant difference between cases and healthy controls for both FADD (p<0.02) and FAS (p<0.007) genes. Conclusions: To the best our knowledge, the data of this study are the first report regarding, the effect of promoter hypermethylation of the FADD and FAS genes in development of OSCC. To confirm the data, it is recommended doing further study in large sample sizes in various genetic populations. Key words:OSCC, FADD, FAS, DNA methylation, gene expression.