Do PPIs Increase the Risk of Colorectal Cancer?

A new study raises questions about long-term PPI use and early-onset colorectal cancer, but the relationship is far from settled. For bariatric patients, the findings are a reminder to periodically review long-term medications and understand the broader implications of obesity-related and co-existing health conditions.

A new study adds to an ongoing debate: is there an association between proton pump inhibitors (PPIs) and colorectal cancer?¹  That new study says yes, but previous research has produced mixed results, leaving important questions unanswered.

PPIs are a commonly prescribed medication for acid reflux, and because they’re often used long-term, they’re also a frequent focus of safety research. At the same time, colorectal cancer rates in younger adults have been rising, and researchers are trying to figure out why.

The latest findings are getting attention, but they need to be interpreted alongside other variables. And we also have to consider the fact that a broader body of evidence has not reached a clear consensus.

What Are PPIs?

Proton pump inhibitors are medications that reduce stomach acid production and are commonly prescribed to treat digestive disorders like acid reflux, GERD, and ulcers. As the name implies, they work by inhibiting the acid-producing “pump” in the stomach lining to alleviate heartburn and upper gastrointestinal irritation.

PPIs are especially relevant for bariatric patients because they’re often prescribed both before and after bariatric surgery. GERD is common in people with obesity, and after procedures such as gastric bypass or sleeve gastrectomy, patients can experience increased acid-related symptoms. It is also a routine practice to be placed on PPIs as a protective measure after surgery to protect the healing digestive tract from stomach acid.

What is the Connection to Cancer?

So, this is where it gets a little confusing. Researchers have investigated whether long-term acid suppression may influence colorectal cancer risk. But, multiple studies have reported conflicting findings. The new study we mentioned has three layers: PPI use, colorectal cancer, and age of onset. Let’s start with what the research says about PPIs and cancer, then we’ll add in the age factor.

First of all, results vary depending on study design and population. In other words, the studies don’t always ask the same question or look at the same groups of people so results can appear mixed.

In one enormous study, over a million people were observed for almost 5 years to compare PPI users with patients taking another type of acid-reducing medication called histamine-2 receptor antagonists (H2RAs). Researchers didn’t see an overall association with an increased risk of colorectal cancer, but what they did note was that the longer someone was on a PPI seemed to correlate with a modest increase in cancer risk.²

A newer study that’s gotten some attention in the last year looked specifically at early-onset colorectal cancer in adults younger than age 50.³ Researchers found an association between long-term PPI use and early-onset colorectal cancer, even after adjusting for other risk factors such as obesity, diabetes, inflammatory bowel disease, and smoking. Important to note with this study was that the researchers found only an association, which does not prove that PPIs directly cause cancer. With that conclusion, they’ve begun to explore what else could be affecting the rates of colorectal cancer, and it may include the gut microbiome.

PPIs reduce stomach acid, which is helpful for conditions like GERD because it decreases irritation from acid exposure. But stomach acid also protects the GI tract and limits the growth of certain bacteria. Long-term acid suppression can cause changes in the balance of bacteria in the digestive tract, a process called gut dysbiosis. Some studies suggest a cascade results from the imbalance that influences inflammatory pathways, immune function, and the environment within the colon in ways that could potentially affect colorectal cancer development.⁴

What Should You Do?

Rather than stopping prescribed medications, patients should focus on understanding their individual colorectal cancer risk factors, maintaining regular follow-up care, and discussing the ongoing need for long-term PPI therapy with their healthcare team. While the latest research suggests a possible association between long-term PPI use and early-onset colorectal cancer, the evidence remains inconclusive, and patients should view these findings as one piece of a much larger picture of colorectal cancer risk.

For obese patients, managing weight through evidence-based treatment has benefits beyond improving appearance or body weight. Obesity is associated with several conditions that can affect digestive health, including GERD, type 2 diabetes, inflammation, and an increased risk for certain cancers in addition to colorectal cancer. Bariatric surgery for the right candidate improves many obesity-related health conditions and reduces the burden of some chronic diseases.

Maintaining a balanced diet with adequate fiber, staying physically active, avoiding tobacco products, limiting alcohol intake, and keeping conditions such as diabetes and high blood pressure well-managed contributes to better health. These are things people can actively work on regardless of whether they take a PPI. Colorectal cancer screening is also a part of prevention and early detection.

At SAMPA, we understand that digestive health, obesity, and chronic conditions often overlap. Our bariatric and colorectal specialists work together with patients to address obesity and obesity-related health conditions and set wellness goals through individualized care plans. If you have questions about your medications, digestive symptoms, or are considering bariatric surgery, give our office a call or contact us online.

References:

1. Strong, C. (2025, October 28). Long-Term PPI Treatment Linked to Higher Risk for Early-Onset CRC Before Age 50. Gastroenterology Advisor. https://www.gastroenterologyadvisor.com/reports/long-term-ppi-linked-to-higher-risk-for-early-onset-crc-before-age-50/.
2. Abrahami, D., McDonald, E. G., Schnitzer, M. E., Barkun, A. N., Suissa, S., & Azoulay, L. (2021). Proton pump inhibitors and risk of colorectal cancer. Gut, 71, 111–118. BMJ. https://doi.org/10.1136/gutjnl-2021-325096.
3. Strong, C. (2025, October 28). Long-Term PPI Treatment Linked to Higher Risk for Early-Onset CRC Before Age 50. Gastroenterology Advisor. https://www.gastroenterologyadvisor.com/reports/long-term-ppi-linked-to-higher-risk-for-early-onset-crc-before-age-50/.
4. Patel, A., Spychalski, P., Antoszewska, M., Regula, J., & Kobiela, J. (2021). Proton pump inhibitors and colorectal cancer: A systematic review. World journal of gastroenterology, 27(44), 7716–7733. https://doi.org/10.3748/wjg.v27.i44.7716.