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). 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. 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). 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.

中文翻译：

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叶酸水平偏高可能会抵消食管鳞状细胞癌和癌前病变中P16和P53基因异常DNA甲基化的影响

这项研究评估了在食管鳞状细胞癌（ESCC）癌变的不同阶段中，叶酸与抑癌基因异常DNA甲基化之间的基因营养相互作用。本研究使用了200例ESCC病例，200例食道癌前病变（EPL）病例和200例年龄（±2岁）和性别相匹配的对照。通过问卷调查收集基线数据和饮食摄入信息。检测p16和p53启动子区域的血清叶酸水平和甲基化状态。血清叶酸水平升高与未甲基化的p16和p53启动子区域的相互作用与降低EPL和ESCC的风险显着相关（相互作用p <0.05）。血清叶酸水平最低的四分位数与p16或p53甲基化的相互作用与ESCC风险增加显着相关（OR = 2.96，95％CI，1.45-6.05； OR = 2.34，95％CI，1.15-4.75）。当发生p16或p53甲基化时，血清叶酸水平升高也与EPL和ESCC风险降低趋势有关。菠菜，大白菜，肝和豆类摄入与未甲基化的p16和p53的相互作用与降低EPL或ESCC的风险显着相关（相互作用p <0.05）。叶酸水平高与未甲基化的p16和p53启动子区域之间的相互作用可能对食道癌变有很强的预防作用。此外，高叶酸水平可能会抵消基因异常DNA甲基化对肿瘤的促进作用，