Abstract 3128: Diet folate, DNA methylation and genetic polymorphisms of MTHFR C677T in esophageal squamous cell carcinoma
Authors: Jianming Wang, Hengchuan Xue, Hongbing Shen
Journal: Cancer Research (2012)

Abstract Background: To explore the role of aberrant hypermethylation of cancer related genes in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiological study in the Chinese population. Methods: This study was conducted in Yangzhong County, an island located on the middle of Yangtze River in the southeast part of Jiangsu Province, China. Totally, 125 ESCC patients having undergone esophagectomy between January 2005 and March 2006 in the Yangzhong People's Hospital were recruited and followed. Face-to-face interviews were conducted by trained investigators using a structured questionnaire. A food frequency questionnaire was used to estimate the dietary intake. For patients having undergone surgery, tissues in the center of the cancer lesion and remote normal appearing esophagus were excised. The methylation at the promoter region of P16, MGMT and hMLH1 was determined by methylation specific PCR. The effects of diet folate, aberrant DNA methylation of selected genes and methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphisms were analyzed. Results: The aberrant CpG island hypermethylation of P16, MGMT and hMLH1 gene could be found in cancer tissues with frequency of about 88.0%, 27.2% and 3.2% respectively, and in remote normal appearing esophageal tissues with frequency of about 36.8%, 11.2% and 0.0% respectively. MGMT gene showed a higher proportion of hypermethylation in cancer tissues while P16 gene showed a higher proportion of hypermethylation in remote normal appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues with odds ratio 3.34 (95% CI:1.07-10.39) and 3.83 (95% CI:1.13-12.94) respectively. Based on the follow-up data, our analysis showed an inverse association between diet folate intake and the risk of death after esophagectomy. The median survival time was 2.92 years for low folate consumption, 3.18 years for moderate folate consumption and over 4.59 years for high folate consumption. After adjusting for potential confounders, the hazard ratios (95% confidence interval) were 0.72(0.36-1.46) for moderate and 0.39(0.20-0.78) for high folate intake, respectively. This preventive effect was more evident in patients carrying MTHFR 677CC genotype. Conclusions: This study indicated the aberrant CpG island hypermethylation of cancer related genes were associated with ESCC and might be a promising biomarker in diagnosis. Diet folate intake may have benefits on the prognosis of ESCC after esophagectomy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3128. doi:1538-7445.AM2012-3128