Intake of Dietary One-Carbon Metabolism-Related B Vitamins and the Risk of Esophageal Cancer: A Dose-Response Meta-Analysis

Abstract

Several B vitamins are essential in the one-carbon metabolism pathway, which is central to DNA methylation, synthesis, and repair. Moreover, an imbalance in this pathway has been linked to certain types of cancers. Here, we performed a meta-analysis in order to investigate the relationship between the intake of four dietary one-carbon metabolism-related B vitamins (B2, B6, folate, and B12) and the risk of esophageal cancer (EC). We searched PubMed, Web of Science, and Embase for relevant studies published through 1 March 2018. The odds ratio (OR) with 95% confidence interval (CI) for the highest versus the lowest level of each dietary B vitamin was then calculated. From 21 articles reporting 26 studies including 6404 EC cases and 504,550 controls, we found an inverse correlation between the consumption of vitamin B6 and folate and the risk of EC; this association was specific to the US, Europe, and Australia, but was not found in Asia. A dose-response analysis revealed that each 100 μg/day increase in folate intake reduced the risk of EC by 12%. Moreover, each 1 mg/day increase in vitamin B6 intake decreased the risk of EC by 16%. Surprisingly, we found that each 1 μg/day increase in vitamin B12 intake increased the risk of esophageal adenocarcinoma by 2%, particularly in the US and Europe, suggesting both geographic and histological differences. Together, our results suggest that an increased intake of one-carbon metabolism-related B vitamins may protect against EC, with the exception of vitamin B12, which should be consumed in moderation.

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

“…Deficiencies of some certain micronutrients, such as folate and vitamin B 6 which are the key methyl donor and cofactor for the enzyme serine hydroxymethyltransferase respectively, have been recognized as the risk factors for cancers including ESCC [7, 8]. Folate and other B vitamins like B 2 , B 6 and B 12 play important roles in the one-carbon metabolism pathway, which is associated with DNA methylation, synthesis and impaired DNA repair [9].…”

“…These cycles require sufficient concentrations of vitamin B 2 and B 12 as cofactors for the enzymes MTHFR and methionine synthase, otherwise folate will become trapped as 5,10-methylenetetrahydrofolate or 5-methyltetrahydrofolate and the generation of methionine will be negatively impacted [11]. However, the association between vitamin B 2 intake and EC risk is not yet entirely understood, and the conclusion has been inconsistent [7]. Several studies illustrated that high intake or plasma concentration of vitamin B 12 were associated with increased risk of cancers including EC [7, 12–14], but the mechanism remains unclear and epidemiological studies have always showed inconsistent findings [8, 15].…”

A Threshold of Objectively-Assessed Daily Sedentary Time for All-Cause Mortality in Older Adults: A Meta-Regression of Prospective Cohort Studies

“…When the lowest category was open-ended, the lower boundary was set to zero. When the highest category was open-ended, we assumed the length of the open-ended interval to be the same as that of the adjacent interval [40,41,42,43,44,45,46,47]. Heterogeneity between studies was evaluated using I 2 (i.e., the proportion of total variation explained by variation between studies).…”

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

“…Accordingly, the intake of these vitamins may induce DNA methylation and gene expression changes and modify the risk of diseases where DNA methylation play an important role such as cancer. In support of this notion, increased intake of vitamins B2, B6, and B12 by humans have been shown to inversely correlate with cancers such as esophageal cancer [146], cervical intraepithelial neoplasia [76], colorectal cancer [104], and prostate cancer [105]. However, the association between vitamin B levels or administration and DNA methylation was only reported in a few studies that measured the joint effect of vitamin B and folic acid status or included vitamin B in a combined model of other vitamins and micronutrients.…”