Proton pump inhibitors and the risk for gastric cancer: possible confounding by serum vitamin B12

We read with interest the article by Cheung et al1 reporting an increased risk of gastric cancer with long-term exposure to proton pump inhibitors (PPI) following Helicobacter pylori (HP) eradication. Several recent reports and a meta-analysis have also demonstrated this association.2 3 The present study, using strict exclusion criteria, was able to adjust for the confounding effect of previous HP infection and eradication, demonstrating a PPI exposure-dependent escalating risk for non-cardia gastric cancer (NCGC) in previously infected patients. The authors suggest that the profound acid suppression by PPIs worsens the atrophic gastritis induced by HP infection, increasing the risk. We wish to address another confounder not taken into consideration in the present study as well as in the previous ones,1–3 namely vitamin B₁₂.

B vitamins are essential for methylation reactions, DNA stability and repair, while intact gastric mucosa and...

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