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Ranitidine Use and Gastric Cancer Among Persons with Helicobacter pylori

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Abstract

Background

The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine.

Aims

We evaluate whether ranitidine use is associated with gastric cancer.

Methods

This is a retrospective multicenter, nationwide cohort study within the Veterans Health Administration, among patients with Helicobacter pylori (HP) prescribed long-term acid suppression with either: (1) ranitidine, (2) other histamine type 2 receptor blocker (H2RB), or (3) proton pump inhibitor (PPI)) between May 1, 1998, and December 31, 2018. Covariates included race, ethnicity, smoking, age, HP treatment, HP eradication. Primary outcome was non-proximal gastric adenocarcinomas, using multivariable Cox proportional hazards analysis.

Results

We identified 279,505 patients with HP prescribed long-term acid suppression (median 53.4 years; 92.9% male). Compared to ranitidine, non-ranitidine H2RB users were more likely to develop cancer (HR 1.83, 95%CI 1.36–2.48); PPI users had no significant difference in future cancer risk (HR 0.92, 95% CI 0.82–1.04), p < 0.001. Demographics associated with future cancer included increasing age (HR 1.18, 95% CI 1.15–1.20, p < 0.001), Hispanic/Latino ethnicity (HR 1.46, 95% CI 1.21–1.75, p < 0.001), Black race (HR 1.89, 95% CI 1.68–2.14) or Asian race (HR 2.03, 95% CI 1.17–3.52), p < 0.001, and gender (female gender HR 0.64, 95% CI 0.48–0.85, p = 0.02). Smoking was associated with future cancer (HR 1.38, 95% CI 1.23–1.54, p < 0.001). Secondary analysis demonstrated decreased cancer risk in those with confirmed HP eradication (HR 0.24, 95% CI 0.14–0.40). No association between ranitidine and increased gastric cancer was found.

Conclusion

There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression.

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Abbreviations

CDW:

Corporate Data Warehouse

FDA:

Food and Drug Administration

H2RB:

Histamine type 2 receptor blockers

HP:

Helicobacter pylori

GC:

Gastric cancer

ICD:

International Classification of Diseases

NDMA:

N-nitrosodimethylamine

OTC:

Over-the-counter

PPI:

Proton pump inhibitor

VHA:

Veterans Health Administration

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Funding

Shria Kumar, MD, MSCE is supported by an NIH training Grant (5 T32 DK 7740-22).

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, PCAM 7S GI, 3400 Civic Center Drive, Philadelphia, PA, 19104, USA

    Shria Kumar & David E. Kaplan

  2. Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA

    David S. Goldberg

  3. Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, USA

    David E. Kaplan

Authors
  1. Shria Kumar
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  3. David E. Kaplan
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Contributions

SK contributed to study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; and statistical analysis. DSG contributed to study concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; statistical analysis; and study supervision. DEK contributed to study concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; statistical analysis; and study supervision.

Corresponding author

Correspondence to Shria Kumar.

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Conflict of interest

SK: Education Conference (Boston Scientific Corporation, Olympus Corporation). DSG: Research grant support (Gilead, Merck, AbbVie, Zydus). DEK: Research grant support (Gilead, Bayer).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. The Institutional Review Board of the Corporal Michael J. Crescenz VA Medical Center approved this study.

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Supplementary Information

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Supplemental Figure 1: Cox proportional hazards, development of gastric cancer by acid suppressant (TIFF 1225 kb)

10620_2021_6972_MOESM2_ESM.tiff

Supplemental Figure 2: Each acid suppressant category prescribed (by percent of total acid suppressants), over time (TIFF 1052 kb)

Supplementary file3 (DOCX 36 kb)

Supplementary file4 (DOCX 34 kb)

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Kumar, S., Goldberg, D.S. & Kaplan, D.E. Ranitidine Use and Gastric Cancer Among Persons with Helicobacter pylori. Dig Dis Sci 67, 1822–1830 (2022). https://doi.org/10.1007/s10620-021-06972-w

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  • DOI: https://doi.org/10.1007/s10620-021-06972-w

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