Prospective study of serum B vitamins levels and oesophageal and gastric cancers in China

Abstract

B vitamins play an essential role in DNA synthesis and methylation, and may protect against oesophageal and gastric cancers. In this case-cohort study, subjects were enrolled from the General Population Nutrition Intervention Trial in Linxian, China. Subjects included 498 oesophageal squamous cell carcinomas (OSCCs), 255 gastric cardia adenocarcinomas (GCAs), and an age- and sex-matched sub-cohort of 947 individuals. Baseline serum riboflavin, pyridoxal phosphate (PLP), folate, vitamin B12, and flavin mononucleotide (FMN) were measured for all subjects. We estimated the associations with Cox proportional hazard models, with adjustment for potential confounders. Compared to those in the lowest quartile of serum riboflavin, those in the highest had a 44% lower risk of OSCC (HR: 0.56, 95% CI: 0.41 to 0.75). Serum vitamin B12 as a continuous variable was observed to be significantly inversely associated with OSCC (HR: 0.95, 95% CI: 0.89 to 1.01, P for score test = 0.041). Higher serum FMN levels were significantly associated with increased risk of OSCC (HR: 1.08, 95% CI: 1.01 to 1.16) and GCA (HR: 1.09, 95% CI: 1.00 to 1.20). Our study prompted that B vitamins have the potential role as chemopreventive agents for upper gastrointestinal cancers.

What have we learned from Linxian esophageal cancer etiological studies?

“…People with a higher level of riboflavin (HR Q4 vs. Q1 0.56, 95% CI 0.41-0.75) or B12 had a significantly lower risk of ESCC. 35 In another investigation on three polymorphisms in two genes that code for enzymes that require folate and B12 as cofactors, MTRR A66G, MTHFR C677T, and MTHFR A1298C, we found that individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/gastric cardia cancer risks (RR 1.45, 95% CI 1.02-2.05) than those with CC or CT genotypes. Compared to subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had a significantly higher risk of ESCC (RR 1.59, 95% CI 1.04-2.42).…”

“…We investigated the associations between B vitamins and related genes with ESCC using serum samples collected in the NIT cohort. People with a higher level of riboflavin (HR Q4 vs. Q1 0.56, 95% CI 0.41–0.75) or B12 had a significantly lower risk of ESCC . In another investigation on three polymorphisms in two genes that code for enzymes that require folate and B12 as cofactors, MTRR A66G, MTHFR C677T, and MTHFR A1298C, we found that individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/gastric cardia cancer risks (RR 1.45, 95% CI 1.02–2.05) than those with CC or CT genotypes.…”

Associations between dietary folate intake and risks of esophageal, gastric and pancreatic cancers: an overall and dose-response meta-analysis

“…Based on our inclusive criteria mentioned in Materials and Methods, 46 articles were eventually included in our meta-analysis. Among all the selected studies, 19 were conducted in patients of esophageal cancer [ 12 - 30 ], 21 were in patients of gastric cancer [ 12 , 14 , 15 , 22 , 26 , 28 , 31 - 45 ] and 12 were in patients of pancreatic cancer [ 46 - 57 ]. Figure 1 shows the eligible selecting process.…”

“…Probands of 4 studies were in American participants [ 15 , 26 , 28 , 29 ], 5 in Chinese [ 12 , 14 , 17 , 19 , 30 ] and 5 in Europeans [ 13 , 16 , 18 , 23 , 27 ]. In terms of the study design, 2 were cohort studies [ 12 , 15 , 18 ] and 17 were case-control studies [ 13 , 14 , 16 - 25 , 58 ].…”

“…Probands of 4 studies were in American participants [ 15 , 26 , 28 , 29 ], 5 in Chinese [ 12 , 14 , 17 , 19 , 30 ] and 5 in Europeans [ 13 , 16 , 18 , 23 , 27 ]. In terms of the study design, 2 were cohort studies [ 12 , 15 , 18 ] and 17 were case-control studies [ 13 , 14 , 16 - 25 , 58 ]. Seven studies clearly reported patients with Esophageal squamous cell cancer (ESCC) [ 12 , 13 , 15 , 17 , 19 - 21 , 23 , 24 , 27 , 28 , 30 ] and six studies were about esophageal adenocarcinoma (EAC) [ 13 , 15 , 16 , 21 , 26 - 28 ].…”