Proton Pump Inhibitor (PPI) Use and Risk of Stomach Cancer

Proton Pump Inhibitor (PPI) Use and Risk of Stomach Cancer

Published on Thursday, November 10, 2022 by Haley McGaha

After going to the doctor and learning that GERD is your official diagnosis, you get prescribed medications (typically PPIs) and go on about your day. 

No big deal. Right?

Something not commonly discussed is the side effects of certain medications and the possible implications they may have later down the road.

I recently wrote an article on GERD and esophageal cancer risk and wanted to keep spreading the word on various cancer types when it comes to GERD or the treatment of GERD.

So, let’s talk about gastric (stomach) cancer.

It is the 5th most common cancer in the world and the 3rd leading cause of cancer-related deaths worldwide. Gastric cancer is typically more common in men than women and is often diagnosed in those ages 65-74.

Depending on the stage of cancer, symptoms can vary.

Symptoms of early-stage stomach cancer include indigestion, nausea, decreased appetite, reflux, and bloating after eating. Symptoms of more advanced stages are bloody stools, vomiting, jaundice, stomach pain, swelling in the stomach from fluid retention, and difficulty swallowing.

Risk factors of stomach cancer include:

H.pylori infections, advanced age, a diet low in fruits/vegetables, a diet high in salted, smoked, or preserved foods, family history of stomach cancer, cigarette smoking, Epstein-Barr virus, chronic atrophic gastritis, and pernicious anemia.

Did you notice that part of the risk factors never mentioned GERD? So, why would I be writing this article on stomach cancer and GERD?

Several research articles have been studying the long-term consequences of medication use for GERD. A study done by Poly et al. looked at several studies and concluded that PPI users were at an increased risk of stomach cancer compared to non-users of PPIs

They also felt that the duration of use was important, noting that long-term use (>3 years) of PPIs was associated with an increased risk of gastric cancer. However, they reported that the findings should be considered with caution due to the variation between studies evaluated (various study designs, definition of PPI use, stomach cancer identification methods, and different potential confounding factors).

In addition to the study done by Poly et al, a 2022 population cohort study done by Abrahami et al., found that PPI users are at a 45% increased risk of gastric cancer compared to new users of H2RAs (another treatment option for GERD).

This study concluded several reasons why PPI use may be associated with a higher risk of gastric cancer. First, PPIs are known to cause hypergastrinemia. Second, long-term PPI use may change the gut microbiota. Third, chronic suppression of acid by PPIs may be connected with atrophic gastritis, one of gastric cancer's main precursors.

Because PPIs have well-established benefits for people, it is important for physicians to regularly assess the benefits for patients, especially for those people who may need long-term PPI treatment for GERD.

If you are struggling with GERD, check out this article on lifestyle changes and diet for the management of GERD. This article is also a great read for additional nutritional considerations with acid reflux and GERD medications.


  1. Surveillance Epidemiology and End Results Program. Cancer stat facts: stomach cancer. National Cancer Institute. Accessed October 25, 2022.
  2. National Cancer Institute. Gastric cancer treatment (PDQ)-health professional version. Accessed October 25, 2022.
  3. Poly, T. N., Lin, M. C., Syed-Abdul, S., Huang, C. W., Yang, H. C., & Li, Y. J. (2022). Proton Pump Inhibitor Use and Risk of Gastric Cancer: Current Evidence from Epidemiological Studies and Critical Appraisal. Cancers, 14(13), 3052. 
  4. Abrahami, D., McDonald, E. G., Schnitzer, M. E., Barkun, A. N., Suissa, S., & Azoulay, L. (2022). Proton pump inhibitors and risk of gastric cancer: population-based cohort study. Gut, 71(1), 16–24. 
  5. Hypergastrinemia: Causes, definition, symptoms & treatment. Cleveland Clinic. (n.d.). Retrieved October 25, 2022, from

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