Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squam
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RESEARCH
Open Access
Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and precancerous lesions Shaokang Wang1*† , Da Pan1†, Ming Su2, Guiling Huang3 and Guiju Sun1
Abstract Background: This study evaluated gene-nutrition interactions between folate and the aberrant DNA methylation of tumor suppressor genes in different stages of carcinogenesis of esophageal squamous cell carcinoma (ESCC). Methods: Two hundred ESCC cases, 200 esophageal precancerous lesion (EPL) cases, and 200 controls matched by age (± 2 years) and gender were used for this study. Baseline data and dietary intake information was collected via questionnaire. The serum folate levels and methylation status of promoter regions of p16 and p53 were detected. Results: The interactions of increased serum folate level with unmethylated p16 and p53 promoter regions were significantly associated with a reduced risk of both EPL and ESCC (p for interaction < 0.05). The interactions of the lowest quartile of serum folate level with p16 or p53 methylation was significantly associated with an increased risk of ESCC (OR = 2.96, 95% CI, 1.45–6.05; OR = 2.34, 95% CI, 1.15–4.75). An increased serum folate level was also related to a decreasing trend of EPL and ESCC risks when p16 or p53 methylation occurred. The interaction of spinach, Chinese cabbage, liver and bean intake with unmethylated p16 and p53 was significantly associated with a reduced risk of EPL or ESCC (p for interaction < 0.05). Conclusions: The interactions between a high folate level and unmethylated p16 and p53 promoter regions may have a strong preventive effect on esophageal carcinogenesis. Additionally, a high folate level may offset the tumor-promoting effects of aberrant DNA methylation of the genes, but it is also noteworthy that a very high level of folate may not have a protective effect on EPL in some cases. Keywords: Esophageal squamous cell carcinoma, Esophageal precancerous lesion, Serum folate, Dietary intake, DNA methylation, Gene-nutrition interaction
* Correspondence: [email protected] † Shaokang Wang and Da Pan contributed equally as co-first authors. 1 Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, P. R. China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is no
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