PPIs and gastric cancer: any causal relationship?

PPIs and gastric cancer: any causal relationship?

Authors

  • Pellegrino Crafa
  • Marilisa Franceschi Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy, Schio (Vi), IT
  • Kryssia Isabel Rodriguez-Castro Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy, Schio (Vi), IT
  • Lorella Franzoni Department of Medicine and Surgery, University of Parma
  • Michele Russo Department of Medicine and Surgery, University of Parma
  • Giovanni Brandimarte Division of Internal Medicine and Gastroenterology, Cristo Re Hospital, Rome, Italy
  • Antonio Tursi Territorial Gastroenterology Service, Azienda Sanitaria Locale Barletta-Andria-Trani, Andria, Italy
  • Massimo Rugge Department of Medicine—DIMED, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
  • Francesco Di Mario Department of Medicine and Surgery, University of Parma

Keywords:

PPIs, Gastric cancer, Atrophic gastritis, Helicobacter pylori, Intestinal metaplasia

Abstract

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid.

Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy.

In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based  focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology.

A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality.  Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer

Author Biography

Pellegrino Crafa

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PPIs and gastric cancer: any causal relationship?. Acta Biomed [Internet]. 2023 Jun. 14 [cited 2024 Jun. 23];94(3):e2023096. Available from: https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/14105