Evaluation of Methylation of MGMT ( <i> O ⁶ </i> -Methylguanine-DNA Methyltransferase) Gene Promoter in Sporadic Colorectal Cancer

Abstract

The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer (CRC). The aim of this study was to demonstrate that MGMT methylation may be one of the candidate mediators of field cancerization in the colon mucosa. Therefore, quantitative methylation-specific polymerase chain reaction was performed on tumor itself and additional samples of 5 and 10 cm away from the tumor in 40 CRC patients. Moreover, colon mucosa was examined from 30 cases with no evidence of cancer as a control. MGMT promoter methylation was present in 27.5% of colorectal tumor specimens. Tumors that showed MGMT promoter methylation had substantial MGMT promoter methylation in their normal adjacent mucosa. The methylation was also observed in 36.36% (4/11) of normal samples with MGMT promoter methylation in the adjacent tumors, in 20.79% (6/29) of samples without MGMT methylation in the adjacent tumors, and in 6.66% (2/30) of control samples (p<0.006 and p<0.001 respectively). Finally, the mean of MGMT methylation levels was significantly higher in the cancerous group than in the control group (6.25±1.702 vs. 0.086±0.036, p<0.001). Some CRCs arise from a field defect defined by epigenetic inactivation of MGMT. Detection of such abnormality may ultimately be useful in risk assessment for CRCs. Epigenetic inactivation of MGMT may lead to colorectal cancer.