| MGMT and TP53 genes play an important role in maintaining genomic stability and protecting cells against mutations or carcinogenesis. This study was carried out to investigate the relationship between genetic and epigenetic alterations in these two genes and esophageal squamous cell carcinoma (ESCC).Methylation of CpG islands in the promoter region of the MGMT gene was determined by methylation specific polymerase chain reaction (MSP) in 119 ESCC specimens, 22 corresponding tissue samples adjacent to the tumors, and 21 normal esophageal epithelial specimens. The levels of MGMT protein in tumors with hypermethylation or unmethylation was analyzed by quantitative immunohistochemistry. All the 21 normal esophageal tissues were shown to be unmethylated in the MGMT gene. However, among the 119 ESCC analyzed, hypermethylation was detected in 46 cases (38.7%). Of the 22 tissues adjacent to the tumors, 5 (22.7%) had this epigenetic alterations. MGMT levels (expressed as median integral light density) in ESCC with promoter hypermethylation was 0.192 (0.01-3.27) which is significantly lower (P = 0.02) than that in the unmethylated ESCC (2.66, 0.07-11.66).A G→T polymorphism located in the -370 bp upstream of the transcriptional start site in MGMT was found by PCR-SSCP and direct sequencing methods. The allele frequencies for the G and T forms of the MGMT gene in Chinese (n = 249) were found to be 0.697 and 0.303, respectively. The distribution of three MGMT genotypes was compared in a case-control study of ESCC. The frequencies of GG, GT, and TT genotypes among controls (n= 249) were 50.6%, 38.1%, and 11.2%, respectively, which were significantly (P = 0.04) different...
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