Ecological associations between gastric acid suppressant use and gastrointestinal cancer incidence: a three-decade global study.

BACKGROUND

Gastric acid suppressants, including proton pump inhibitors (PPIs) and histamine H2-receptor antagonists, are widely used globally. Their long-term safety remains a concern, particularly regarding gastrointestinal cancer risks.

AIMS

To assess population-level associations between gastric acid suppressant use and the incidence of major gastrointestinal cancers, adjusting for potential confounders.

METHODS

This ecological panel study analyzed country-year data from 24 nations (1990-2020). Consumption of acid suppressants (ATC A02B, DDD/1000/day) was obtained from OECD Health Statistics. Age-standardized cancer incidence rates (colorectal, liver, pancreatic, esophageal) were sourced from the GBD 2019 dataset. Multivariable linear mixed-effects models were adjusted for dietary risks, BMI, tobacco, alcohol, antibiotics, NSAIDs, and GDP per capita.

RESULTS

Higher acid suppressant use was significantly associated with increased liver cancer (β = 0.0086; 95% CI 0.0019 to 0.0154; p = 0.0136) and pancreatic cancer (β = 0.0148; 95% CI 0.0068 to 0.0227; p = 0.0004) incidence. No significant associations were found for colorectal or esophageal cancers. Model fit was strongest for liver and pancreatic outcomes.

CONCLUSIONS

While causal inference cannot be drawn from ecological data, the findings suggest a population-level association between gastric acid suppressant consumption and increased liver and pancreatic cancer incidence. These results support the need for cautious prescribing and further research using individual-level data.