Introduction
Proton pump inhibitors, or PPIs, are medications that help to lower the production of stomach acid. An increasing amount of research from epidemiological studies suggests that PPIs are linked to the recurrence of GERD (gastroesophageal reflux disease) related problems like peptic stricture, esophageal ulcers, and bleeding. Consequently, it is thought that using PPIs to avoid acid-related problems and heartburn is a safe and efficient treatment option. Concerns have been expressed by several medical professionals over the potential for major side effects, including stomach cancer, with prolonged PPI use. Long-term PPI use has been linked to a higher risk of stomach cancer, even in cases where Helicobacter pylori has been successfully eradicated, according to recent epidemiological research.
What Is a Proton Pump Inhibitor?
Proton Pump Inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are two examples of acid suppression medications frequently administered to treat the symptoms of various stomach disorders. PPIs' improved acid suppression and perceived safety profile have increased their use in recent years.
Proton pump inhibitors are a class of drugs that treat many different diseases associated with the production of acid in the stomach. The most powerful acid inhibitors ever created are Proton Pump Inhibitors (PPIs), which work by preventing parietal cells' H+/K+ ATPase from functioning. Due to their potent acid-inhibitory properties, PPIs are frequently prescribed as the preferred medication for the management of GERD and medication-induced peptic ulcers. Long-term PPI use may help with the best management of GERD along with serious side effects such as esophageal stricture. Even for patients with mild GERD, long-term PPI prescriptions are frequently chosen as maintenance therapy.
How Does Proton Pump Inhibitor Cause Gastric Cancer?
The most likely explanation for the link between long-term PPI use and the onset of gastric cancer is hypergastrinemia, which is brought on by a decrease in stomach acid output. This decrease in acidity then leads to the establishment of Neuroendocrine Tumors (NETs) and the growth of enterochromaffin-like cells (ECL cells), which express gastric cholecystokinin-2 (CCK-2) receptors and are the cells that gastrin targets in the oxyntic mucosa (cells specialized for digestion). Long-term use of PPIs and other anti-acidic medicines can produce gastric hypochlorhydria (reduced secretion of hydrochloric acid), preventing the somatostatin-mediated negative feedback of gastrin release on antral G-cells. This can lead to hypergastrinemia (increased secession of gastrin, a hormone that helps in digestion) and hyperplasia (increased multiplication of cells) of the gastric mucosa or ECL (enterochromaffin-like) cells.
The second theory is that, in hypergastrinemic circumstances like chronic atrophic gastritis or prolonged PPI usage, gastrin itself has a trophic impact on both the oxyntic mucosa and ECL cells. However, compared to gastric NET, generally, a molecular connection between ECL cell hyperplasia and stomach adenocarcinoma is less significant. However, ECL cells are the source of some stomach adenocarcinomas. ECL cell markers, such as chromogranin A, synaptophysin, histidine decarboxylase, and neuron-specific enolase, were found to be more highly expressed in diffuse-type gastric cancer as opposed to intestinal-type gastric cancer in a prior study employing human gastric carcinoma tissues. Additionally, several pathologic investigations have demonstrated that most Periodic Acid-Schiff (PAS)-positive signet ring cell carcinomas expressed ECL-cell markers in abundance but not mucin. This suggests that the development of signet ring cell carcinoma may result from the dedifferentiation of ECL cells into signet ring cells with PAS-positive cytoplasm.
The impact of PPIs as of right now could be summed up by saying this. Theoretically, PPIs may contribute to the development of H. pylori-associated gastric carcinogenesis or at least decrease gastric acid production by reducing stomach acid secretion and causing hypergastrinemia due to the growth of ECL cells in the oxyntic gland. This theory, however, frequently falls short of explaining the mechanism underlying PPI-induced stomach carcinogenesis. Furthermore, a recent important translational study revealed that patients with H. pylori-induced atrophic gastritis displayed a decreased bacterial abundance and diversity, while PPI-treated patients displayed equivalent microbial diversity to normal people. According to this research, PPIs have no discernible effects on the microbiota of the stomach or on the risk of developing stomach cancer.
How Can the Risk of Gastric Cancer Be Reduced?
Experts recommend that those using PPIs speak with their physician regarding their prescription. They recommend that patients should not abruptly stop PPI use. This is mainly because after abruptly cutting them off, people frequently have rebound symptoms. PPIs may not be necessary for patients with GERD if they make dietary and lifestyle changes, such as quitting smoking, cutting back on alcohol and caffeine, avoiding spicy foods, and eating no later than noon. Altering a patient's diet and lifestyle should be the cornerstone of any treatment plan for acid reflux. However, in certain cases, if that is ineffective, the patient may require long-term proton pump inhibitor medication. Ultimately, though, the choice of whether to keep taking the medication should be decided after seeing a physician. When it comes to long-term PPI use, patients should consult their doctors and heed their advice regarding whether to continue taking the medication or switch to another treatment.
According to meta-analyses, aspirin lowers the incidence of stomach cancer without taking H. pylori status into account. In those who have had their H. pylori removed, aspirin has been linked to a decreased incidence of stomach cancer. Aspirin use seems to offset any potential negative impact of PPIs on gastric cancer.
Conclusion
There is growing evidence from numerous observational studies that long-term PPI use is linked to an increased risk of developing stomach cancer. But only those with a history of H. pylori infection, either active or old, and especially those with underlying precancerous stomach lesions, are probably in danger. Instead of not prescribing PPIs to patients who have legitimate causes, like Barrett's esophagus or a high risk of upper gastrointestinal bleeding, doctors should consider the patient's risk-benefit profile before writing a prescription. This is especially crucial for aspirin users who are more susceptible to upper gastrointestinal bleeding since aspirin may counteract any negative impact that PPIs may have on the development of gastric cancer.
