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 International

Ming Su¹  Pengfei Luo²  Guiling Huang³  Ting Zhang⁴  Lingmeng Fu⁴  Guiju Sun⁴  Da Pan⁴  Jie Wei⁴  Shaokang Wang⁴ 

[1]Huai’an District Center for Disease Control and Prevention

[2]Jiangsu Provincial Center for Disease Control and Prevention

[3]Jiangsu Vocational College of Medicine

[4]Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University

关键词: Esophageal squamous cell carcinoma;    Esophageal precancerous lesion;    Methylenetetrahydrofolate reductase;    Vitamin B2;    Vitamin B12;    DNA methylation;   

DOI  :  10.1186/s12935-019-1012-x

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown