Chronic Proton Pump Inhibitors May Increase Cancer Risk  

Proton pump inhibitors (PPIs): One in ten takes them, they are available without a prescription in many countries, so are they really safe?

This is one question we are trying to answer with our research at the Centre for Translational Microbiome Research at the Karolinska Institutet in Stockholm, Sweden.

PPIs, such as omeprazole, are among the most commonly-used drugs worldwide, usually via prescription but also available over-the-counter in many countries. Our research showed that one in ten Swedish adults are using these drugs over a longer period of time, not counting occasional users or people who get it without a prescription. So that is a lot.

People, of course, take them for a reason, including reflux-symptoms, heartburn, or other stomach problems, but PPIs are also prescribed to protect your stomach against developing peptic ulcers when using aspirin or anti-inflammatory drugs, notorious for causing damage to your stomach mucosa, which can create peptic ulcers.

So, without a doubt, PPIs can save lives if bleeding peptic ulcers can be prevented and treated. PPIs are also believed to have long-term benefits, since reflux is a major risk factor for developing one of the 2 major types of esophageal cancer, esophageal adenocarcinoma. So treating reflux should reduce the risk of developing this type of cancer. So far, so good…

Yet, drugs, diet, and other environmental factors are also influencing our microbiome, which includes the microbes in our gut needed to digest our food and keep us healthy. Recent research indicated that when you use PPIs over a longer period of time, there will be different microbes striving in your gut – and no other drug (even antibiotics) seemed to have such a large effect based on the stool of large groups of individuals (1). In other words, PPIs seem to promote the survival of other microbes in the gut than in people not taking PPIs, probably eliminating some bacteria which protect us against harmful bacteria and infections, but the exact effect on our health is not entirely clear yet.

In our 2 recently published projects (2, 3), we looked at chronic PPI use and the risk of cancer, based on the large population-based data sets in Sweden. We compared all adults taking at least 6 months of PPIs during the study period (2005-2012), and compared their risk of developing stomach and esophageal cancer with the cancer risk in the entire adult Swedish population. We looked at different indications of use to distinguish if the effect of the medication from the reason why people took PPIs.

For people with reflux, we expected a higher risk of esophageal cancer, since even with treatment, the risk of cancer will probably remain higher than someone who never had reflux. Yet, our findings also suggested that the risk of these cancer types may be higher among those using PPIs to protect their stomach and had no reported stomach problems. The risk seemed to be highest among young individuals (< 40 years), but we need to note that gastric and esophageal cancer are anyway rare at that age.

When looking at large populations, there are without doubt many factors which may influence the associations being studies – so we cannot prove causality (“A causes B”) based on a handful of studies (4). We controlled our results for age, sex and year of diagnosis – but could not compare the risk of PPI-users with people who are on all points similar except for the PPI use. Since PPIs are the number one drug in the gastro-intestinal field, virtually everyone has been using PPIs at a certain point just because these drugs are so effective. In Sweden, PPI use was 30-40 times more common than the number 2 drug for these indications, the histamine-2-receptor antagonists (such as cimetidine).

Since other groups have been publishing findings similar to ours assessing the risks related long-term PPI use, considering stomach cancer and also other cancer types but also other long-term effects, there is certainly smoke, but we are not sure yet that there is a fire. So we certainly do not recommend to stop any PPI treatment without consulting a physician. Yet, we do want to raise awareness about potential long-term effects and uncontrolled over-the-counter use. So maybe treatment should be reserved for stricter indications or at least restricted in time.

Maybe one should invest more in alternative non-medical treatment options, but we realize it does take more time and effort to lose weight and incorporate a healthier lifestyle and diet than taking a pill.

These findings are described in the article entitled Maintenance proton pump inhibition therapy and risk of oesophageal cancer, recently published in the journal Cancer EpidemiologyThis work was conducted by Nele Brusselaers, Lars Engstrand, and Jesper Lagergren from Karolinska Institutet.


  1. Imhann F, Vich Vila A, Bonder MJ, Lopez Manosalva AG, Koonen DPY, Fu J, et al. The influence of proton pump inhibitors and other commonly used medication on the gut microbiota. Gut microbes. 2017 Jul 4;8(4):351-8. PubMed PMID: 28118083. Pubmed Central PMCID: PMC5570416. Epub 2017/01/25. eng.
  2. Brusselaers N, Engstrand L, Lagergren J. Maintenance proton pump inhibition therapy and risk of esophageal cancer. Cancer epidemiology. 2018 Apr;53:172-7. PubMed PMID: 29477057.
  3. Brusselaers N, Engstrand L, Lagergren J. PPI use and esophageal cancer: What if the results are true? Cancer epidemiology. 2018 Apr 9. PubMed PMID: 29650437.
  4. Brusselaers N, Engstrand L, Lagergren J. PPI use and esophageal cancer: What if the results are true? Cancer epidemiology. 2018 Jun;54:139-40. PubMed PMID: 29650437.

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