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.
Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation/genetics , Intestinal Mucosa/pathology , O(6)-Methylguanine-DNA Methyltransferase/genetics , Promoter Regions, Genetic/genetics , Adult , Aged , DNA/genetics , DNA Repair/genetics , Female , Humans , Intestinal Mucosa/metabolism , Male , Middle AgedABSTRACT
BACKGROUND: Previous studies have shown that upper gastrointestinal cancers are the most common cancers in Caspian Littoral, and rate of esophageal cancer (EC) in Iranian Turkmens residing in the Eastern part of littoral are among the highest in the world. Our aim was to reassess the rate 30 years later and following socioeconomic changes in the region. METHODS: A comprehensive retrospective search was undertaken to find all new cancer cases during the 1996-2000 period. Diagnosis of cancer was based on histopathological reports in 68.2%, clinical and/or radiological evidence in 29.7% and death certificate only (DCO) in 2.1% of the cases. RESULTS: A total of 5143 new cancer cases were registered of whom 3063 (59.6%) were males. The median (IQR) age was 60 (44-69) years. Age-standardized rates (ASR) for all cancers in males and females were 134.7 and 104.5 per 100,000, respectively. Based on ASR, the top five common cancers in males (excluding skin cancer) were cancers of esophagus (43.4), stomach (27.8), colorectal (10.7), bladder (7.8) and oral cavity (6.3), while in females cancer of esophagus (36.3) was followed by cancers of breast (15.7), stomach (8.3) colorectal (6.6) and cervix (3.6). CONCLUSION: We conclude that EC incidence rate has decreased to less than half the rate reported 30 years ago, while the incidence rates of colorectal and breast cancers have increased significantly.
