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-control study

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

doi:10.1186/s12935-019-1012-x

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-control study

Cancer Cell Int. 2019 Nov 12:19:288. doi: 10.1186/s12935-019-1012-x. eCollection 2019.

Authors

Da Pan¹, Ming Su², Guiling Huang³, Pengfei Luo⁴, Ting Zhang¹, Lingmeng Fu¹, Jie Wei¹, Shaokang Wang¹, Guiju Sun¹

Affiliations

¹ 1Key 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 People's Republic of China.
² Huai'an District Center for Disease Control and Prevention, Huai'an, 223200 People's Republic of China.
³ 3Jiangsu Vocational College of Medicine, Yancheng, 224005 People's Republic of China.
⁴ 4Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009 People's Republic of China.

Abstract

Background: The 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).

Methods: 200 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.

Results: The 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).

Conclusions: The 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.

Keywords: DNA methylation; Esophageal precancerous lesion; Esophageal squamous cell carcinoma; Methylenetetrahydrofolate reductase; Vitamin B12; Vitamin B2.