Low Vitamin B12 Increases Risk of Gastric Cancer: A Prospective Study of One-Carbon Metabolism Nutrients and Risk of Upper Gastrointestinal Tract Cancer

Abstract

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed pre-diagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin, and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988.

We conducted a nested case-control study including 127 non-cardia gastric adenocarcinoma (NCGA), 41 esophago-gastric junctional adenocarcinoma (EGJA), and 60 esophageal squamous cell carcinoma (ESCC) incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection, and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower pre-diagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7 to 12.6 for lowest compared to highest quartile, p-trend < 0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population.

As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen. This article is protected by copyright. All rights reserved.

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