MTHFR C677T genetic polymorphism in combination with serum vitamin B2, B12 and aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and esophageal precancerous lesions: a case\u2013control study

Da Pan,Pengfei Luo,Ting Zhang,Shaokang Wang,Jie Wei,Guiju Sun,Lingmeng Fu,Ming Su,Guiling Huang

doi:10.1186/s12935-019-1012-x

Abstract

BackgroundThe study aimed to explore the associations between the interactions of serum vitamin B2 or B12 levels, aberrant DNA methylation of p16 or p53 and MTHFR C677T polymorphism and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal precancerous lesion (EPL).Methods200 ESCC cases, 200 EPL cases and 200 normal controls were matched by age (± 2 years) and gender. Serum vitamin B2 and B12 levels, MTHFR C677T genetic polymorphisms and the methylation status of genes were assessed. Chi square test, one-way analysis of variance and binary logistic regression were performed.ResultsThe lowest quartile of both serum vitamin B2 and B12 with TT genotype showed significant increased EPL risk (OR = 4.91, 95% CI 1.31–18.35; OR = 6.88, 95% CI 1.10–42.80). The highest quartile of both serum vitamin B2 and B12 with CC genotype showed significant decreased ESCC risk (OR = 0.16, 95% CI 0.04–0.60; OR = 0.10, 95% CI 0.02–0.46). The ORs of p16 methylation for genotype CT and TT were 1.98 (95% CI 1.01–3.89) and 17.79 (95% CI 2.26–140.22) in EPL, 4.86 (95% CI 2.48–9.50) and 20.40 (95% CI 2.53–164.81) in ESCC, respectively. Similarly, p53 methylation with genotype TT was associated with increased EPL and ESCC risks (OR = 13.28, 95% CI 1.67–105.70; OR = 15.24, 95% CI 1.90–122.62).ConclusionsThe MTHFR C677T genotype and serum vitamin B2 or B12 levels may interact in ways which associated with the EPL and ESCC risks. The gene–gene interaction suggested that aberrant DNA methyaltion of either p16 or p53 combined with T alleles of MTHFR was associated with increased risks of both EPL and ESCC.

Highlights

The study aimed to explore the associations between the interactions of serum vitamin B 2 or B12 levels, aberrant DNA methylation of p16 or p53 and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal precancerous lesion (EPL)
Serum vitamin B 2 and B12 levels of the subjects The distributions of serum vitamin B 2 and B12 levels in normal controls, EPL cases and ESCC cases are shown in Table 2 and Fig. 1
Our study suggested that: firstly, healthy controls were more likely to have higher levels of vitamin B2 and B12 than ESCC cases; secondly, variant genotype TT and the T allele were associated with significantly increased risk of EPL; thirdly, the MTHFR C677T genotype may modify association between

Summary

Introduction

The study aimed to explore the associations between the interactions of serum vitamin B 2 or B12 levels, aberrant DNA methylation of p16 or p53 and MTHFR C677T polymorphism and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal precancerous lesion (EPL). The two histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have almost completely distinct etiologic and pathologic characteristics, geographic patterns, time trends and major risk factors [2]. Moderate and severe esophageal squamous dysplasia, the recognized esophageal precancerous lesions (EPL) for ESCC, are associated with approximately 3-, 10-, and 30-fold higher risk of ESCC than normal [3,4,5]. Studies illustrated that some risk or protective factors may be similar for both EPL and ESCC [6]

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Discussion

Conclusion