From the Guidelines
Proton Pump Inhibitors (PPIs) do not have a direct, proven link to an increased incidence of gastric cancer, as the current evidence suggests that eradication of H. pylori in patients receiving long-term PPIs does not reduce the risk of gastric cancer 1. The relationship between PPI use and gastric cancer risk is complex and influenced by various factors, including the presence of H. pylori infection, the duration of PPI therapy, and individual patient risk factors.
- Key considerations include:
- The potential for PPI-induced hypergastrinemia, which could theoretically promote cellular proliferation in the stomach lining
- Changes to the gastric microbiome due to reduced acid production
- The possibility that PPIs may mask symptoms of early gastric cancer, leading to delayed diagnosis
- For patients requiring long-term acid suppression, strategies to mitigate potential risks include:
- Using the lowest effective PPI dose
- Periodic reassessment of the need for continued therapy
- Considering H2 blockers as alternatives when appropriate
- Patients with additional risk factors for gastric cancer, such as H. pylori infection, family history, or certain genetic conditions, should discuss monitoring strategies with their healthcare provider, as the evidence does not support a direct link between PPI use and increased gastric cancer incidence 1. The most recent and highest quality study, the Maastricht IV/Florence Consensus Report from 2012, provides a Grade A recommendation that eradication of H. pylori in patients receiving long-term PPIs does not reduce the risk of gastric cancer 1.
From the Research
Incidence of Gastric Cancer with Proton Pump Inhibitors (PPIs)
- The incidence of gastric cancer with PPIs is a topic of ongoing research and debate 2, 3, 4, 5, 6.
- A study published in 2022 found that long-term PPI use is associated with an increased risk of gastric cancer, with a pooled risk ratio of 1.80 (95% CI, 1.46−2.22, p < 0.001) 4.
- Another study published in 2018 found that long-term use of PPIs was associated with an increased risk of gastric cancer, with a hazard ratio of 2.44 (95% CI, 1.42 to 4.20) 6.
- The risk of gastric cancer increased with duration of PPI use, with hazard ratios of 5.04,6.65, and 8.34 for ≥1 year, ≥2 years, and ≥3 years of use, respectively 6.
- A review of literature and pathophysiological mechanisms published in 2016 discussed the potential link between PPI use and gastric cancers, including gastric neuroendocrine tumors and gastric adenocarcinomas 5.
- However, a study published in 2020 found that long-term use of PPIs did not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment 2.
Quantifying the Increase in Gastric Cancer Incidence
- The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess gastric cancers (95% CI, 1.25 to 9.54) per 10,000 person-years 6.
- The pooled risk ratio for developing gastric cancer in patients receiving PPIs was 1.80 (95% CI, 1.46−2.22, p < 0.001) 4.
- The hazard ratio for gastric cancer associated with long-term PPI use was 2.44 (95% CI, 1.42 to 4.20) 6.