Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 1;32(9):1174-1181.
doi: 10.1158/1055-9965.EPI-23-0241.

Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project

Michele Sassano  1   2 , Marco Mariani  2 , Claudio Pelucchi  3 , Nuno Lunet  4   5   6 , Samantha Morais  4   5   6 , Vicente Martín  7   8 , Victor Moreno  8   9   10   11 , Maria Paula Curado  12 , Emmanuel Dias-Neto  12 , Marcis Leja  13   14   15   16 , Evita Gašenko  14   15   16 , Carlo La Vecchia  3 , Stefania Boccia #  2   17 , Roberta Pastorino #  17
Affiliations

Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project

Michele Sassano et al. Cancer Epidemiol Biomarkers Prev. .

Abstract

Background: A potential association between proton-pump inhibitors (PPI) and gastric cancer remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Pooling (StoP) Project.

Methods: Data from five case-control studies of the StoP Project were included (1,889 cases and 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modeled the dose-response relationship between the cumulative duration of PPI intake and gastric cancer.

Results: Significant associations between PPI intake and gastric cancer, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall odds ratio (OR) for any reported PPI intake was 1.78 [95% confidence interval (CI): 0.76-4.14]. In the dose-response analysis, the ORs of gastric cancer were found to be higher for short durations of PPI intake (6 months: OR 3.26; 95% CI: 2.40-4.42; one year: OR 2.14; 95% CI: 1.69-2.70; 2 years: OR 1.50; 95% CI: 1.22-1.85; 3 years: OR 1.27; 95% CI: 1.03-1.56), with the association becoming not significant for durations longer than 3 years.

Conclusions: Our findings suggest that the observed association between PPIs and gastric cancer might be mainly due to reverse causality.

Impact: The results of this study suggest that PPIs are a safe therapeutic choice regarding their effect on the occurrence of gastric cancer. See related commentary by Richman and Leiman, p. 1127.

PubMed Disclaimer

Figures

Figure 1. Pooled adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between intake of proton-pump inhibitors and gastric cancer, overall and stratified by selected study participants’ demographic characteristics (sex and age). In all analyses, study participants were considered not exposed if they did not report intake of PPIs.
Figure 1.
Pooled adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between intake of proton-pump inhibitors and gastric cancer, overall and stratified by selected study participants’ demographic characteristics (sex and age). In all analyses, study participants were considered not exposed if they did not report intake of PPIs.
Figure 2. Pooled adjusted ORs and corresponding 95% CIs for the association between intake of proton-pump inhibitors and gastric cancer, by subsite and histologic type. In all analyses, study participants were considered not exposed if they did not report intake of PPIs.
Figure 2.
Pooled adjusted ORs and corresponding 95% CIs for the association between intake of proton-pump inhibitors and gastric cancer, by subsite and histologic type. In all analyses, study participants were considered not exposed if they did not report intake of PPIs.
Figure 3. Dose–response relationship between intake of proton-pump inhibitors (PPI) and gastric cancer fitted by using a one-stage logistic mixed-effects model with fractional polynomial (n = 4,575). Solid black line: log odds ratio; dashed black line: 95% confidence interval; solid horizontal gray line: odds ratio = 1.
Figure 3.
Dose–response relationship between intake of proton-pump inhibitors (PPI) and gastric cancer fitted by using a one-stage logistic mixed-effects model with fractional polynomial (n = 4,575). Solid black line: log odds ratio; dashed black line: 95% confidence interval; solid horizontal gray line: odds ratio = 1.
See this image and copyright information in PMC

Comment in

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49. - PubMed
    1. Zhou XLL, Xue WHH, Ding XFF, Li LFF, Dou MMM, Zhang WJJ, et al. . Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies. Oncotarget 2017;8:55622–31. - PMC - PubMed
    1. Weltermann T, Schulz C, Macke L. Effect of frequently prescribed drugs on gastric cancer risk. Best Pract Res Clin Gastroenterol 2021;50–51:101741. - PubMed
    1. Ahn JS, Eom CS, Jeon CY, Park SM. Acid suppressive drugs and gastric cancer: a meta-analysis of observational studies. World J Gastroenterol 2013;19:2560–8. - PMC - PubMed
    1. Lundell L, Vieth M, Gibson F, Nagy P, Kahrilas PJ. Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology. Aliment Pharmacol Ther 2015;42:649–63. - PubMed

Publication types

MeSH terms

Substances