Proton pump inhibitors and risk of gastric cancer: a population-based cohort study

Abstract

Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990Denmark, during -2003. We compared incidence rates among new users of PPI (n ¼ 18 790) or histamine-2-antagonists (H2RAs) (n ¼ 17 478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8 -2.0) among PPI users and 1.2 (95% CI: 0.8 -1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or nonusers. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.

Obesity and related risk factors in gastric cardia adenocarcinoma

“…Additionally, the data on prescription use was based on the prescription being written rather than necessarily filled. Nevertheless, the results are provocative and consistent with another study [38] showing a weak association between acid-suppressing medication use and total number of gastric cancer cases, not broken down by anatomical subsite. A mechanistic link between the use of these medications and gastric carcinogenesis is conceivable, on the basis of the moderately elevated gastrin levels frequently found in users of these drugs and the trophic (proproliferative) effects of gastrin on the gastrointestinal mucosa [39].…”

3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

“…One epidemiological study suggests that prolonged use (more than 1 year) of proton pump inhibitors might be associated with increased gastric cancer risk (159) . Prolonged use and high doses of antisecretories in an animal model has been capable of promoting adenocarcinoma development in H pylori infected animals, strengthening the recommendation for it to be eradicated as a measure of preventing gastric cancer in this group of individuals (see below) (88,132) .…”

Could proton pump inhibitors cause cancer?

“…Not included in these possible complications was esophageal adenocarcinoma, which was rare two or three decades ago, but has had such a dramatic and progressive rise in recent years [2,3] that it has now been described as an 'epidemic' [4]. The authors state there is no explanation for this, but the fact that this escalation started with the advent of PPIs in the late 1980s and mirrors their increased sales may be more than coincidence.…”