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.

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an IC 50 of 70.7±1.72μM at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose-and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.

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.

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