One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC. One-carbon metabolism (OCM) refers to a series of biochemical reactions essential for DNA methylation, synthesis, and repair. These reactions are often catalyzed by enzymes and cofactors derived from B vitamins, and B vitamin deficiency has been linked to cancer. Here, the authors investigated the relationship between B vitamin deficiency and risk of esophageal and gastric cancers in Iran, where the incidence of these cancers is high. Elevated levels of plasma biomarkers that indicate vitamin B6 and B12 deficiency were associated with higher risk of esophageal and gastric cancers, they found. Improving vitamin intake could reduce the incidence of these cancers in the populations with high prevalence of vitamin B deficiency. image