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http://dx.doi.org/10.7314/APJCP.2012.13.10.5303

Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism and Folate Intake in Esophageal Squamous Cell Carcinoma  

Chen, Jing (Department of Cadre Ward, the General Hospital of Chengdu Military Area)
Huang, Zhi-Jie (Department of Nuclear Medicine, the General Hospital of Chengdu Military Area)
Duan, Yu-Qin (Department of Cadre Ward, the General Hospital of Chengdu Military Area)
Xiao, Xin-Rong (Department of Cadre Ward, the General Hospital of Chengdu Military Area)
Jiang, Jian-Qing (Gastrointestinal Surgery, the General Hospital of Chengdu Military Area)
Zhang, Ru (Department of Cadre Ward, the General Hospital of Chengdu Military Area)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.10, 2012 , pp. 5303-5306 More about this Journal
Abstract
Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. Methods: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR-restriction fragment-length polymorphism (PCR-RFLP). Results: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57). Conclusion: Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.
Keywords
DNA methylation; P16; MGMT; hMLH1; MTHFR; esophageal squamous cell carcinoma;
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