"Long-term Use of Proton Pump Inhibitors Increases Risk of Gastrointestinal Cancer"

Professor Myeong Seung-kwon, Graduate School of Cancer Science and Policy
"Lifestyle Improvements Needed to Reduce PPI Use"

A study has found that long-term use of proton pump inhibitors (PPIs), acid secretion suppressants used to treat gastroesophageal reflux disease and gastroduodenal ulcers, increases the risk of gastrointestinal cancers.

[Image provided by Pixabay]

The National Cancer Center announced on the 20th that Professor Myeong Seung-kwon of the Graduate School of International Cancer Studies conducted a meta-analysis of 25 cohort studies published in international journals from 2018 to 2022, confirming these results.

PPIs, acid secretion suppressants, have been the most commonly prescribed drugs since 1989 for treating gastrointestinal diseases such as gastroesophageal reflux disease, which causes heartburn and acid reflux symptoms due to stomach acid flowing back into the esophagus, and gastroduodenal ulcers. Patients with gastroesophageal reflux disease typically take PPIs for 4 to 8 weeks, but without lifestyle improvements such as addressing obesity, overeating, smoking, excessive alcohol consumption, or coffee intake, the condition often becomes chronic, leading to long-term use.

Professor Myeong conducted a meta-analysis by synthesizing the results of 25 cohort studies finally selected through literature searches in major medical databases PubMed and EMBASE.

The analysis showed that people who took PPIs had about twice the risk of gastrointestinal cancer compared to those who did not take the medication. Among gastrointestinal cancers, the risk of most types?including stomach cancer, esophageal cancer, pancreatic cancer, liver cancer, gallbladder, and bile duct cancers?significantly increased, except for colorectal cancer. The risk of gastrointestinal cancer was about five times higher when the medication was taken for less than one year, and about 1.7 times higher when taken for up to three years.

Professor Myeong, the lead author of the study, said, "For several years, cohort studies have started to report an increased risk of gastrointestinal cancers such as stomach and esophageal cancer with long-term PPI use. Of course, some cohort studies have found no significant association, which is why we conducted this meta-analysis synthesizing cohort studies."

Professor Myeong explained that biological mechanisms by which PPIs increase the risk of gastrointestinal cancer have been proposed. He said, "Laboratory and animal studies have shown that PPIs stimulate G cells in the stomach and duodenum to increase the secretion of a hormone called gastrin. Elevated blood gastrin levels stimulate specific receptors on gastric mucosal cells, which can promote cancer development. Additionally, PPIs increase bacterial colonization in the gastrointestinal tract, leading to increased nitrosamines, carcinogenic substances that can cause gastrointestinal cancers."

However, there is also the possibility of reverse causation, where PPI use followed the onset of cancer. Professor Myeong noted, "It is possible that patients took PPIs because of gastrointestinal symptoms such as heartburn before a diagnosis of gastrointestinal cancer. While randomized controlled trials, which provide higher levels of evidence than observational cohort studies, are needed to confirm these results, there are many ethical limitations to conducting such clinical trials."

Professor Myeong advised that lifestyle improvements are necessary to reduce PPI use. He said, "Currently, it is important to improve lifestyle factors that cause gastroesophageal reflux disease?such as obesity, overeating, smoking, excessive alcohol consumption, and coffee intake?to reduce PPI use. Regarding these study results, I believe discussions on PPI use are needed within the relevant professional societies."

This study was published online on the 20th of last month in the oncology SCIE international journal Oncology Letters, with Tien Hoang Tran, a graduate student from Vietnam at the National Cancer Center Graduate School of International Cancer Studies, as the first author, and Professor Myeong Seung-kwon as the corresponding author.

Myung Seung-kwon, Dean of the Graduate School of International Cancer Graduate School.
[Photo by National Cancer Center]

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