Proton Pump Inhibitors and Likelihood of Colorectal Cancer in the Korean Population: Insights from a Nested Case-Control Study Using National Health Insurance Data

Abstract

The potential connection between proton pump inhibitors (PPIs) and colorectal cancer (CRC) risk remains unclear, with specific ethnic genetic backgrounds playing a role in PPI-induced adverse effects. In this nested case-control study, we investigated the risk of CRC in relation to preceding PPI use and the duration of use using data from the Korean National Health Insurance Service-National Sample Cohort database, including 9374 incident CRC patients and 37,496 controls. To assess the impact of preceding PPI exposure (past vs. current) and use duration (days: <30, 30-90, and ≥90) on incident CRC, we conducted propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounding factors. Our findings revealed that past and current PPI users had an increased likelihood of developing CRC. Regardless of duration, individuals who used PPIs also had higher odds of developing CRC. Subgroup analyses revealed that CRC occurrence increased independent of history or duration of prior PPI use, consistent across various factors such as age, sex, income level, and residential area. These findings suggest that PPI use, regardless of past or present use and duration of use, may be related to an increased risk of developing CRC in the Korean population.

Keywords: colorectal cancer; national healthcare data; nested case–control study; proton pump inhibitor.

Figure 1

Schematic diagram of the participant selection process used in this study. Of 1,137,861 participants, 9374 participants with colorectal cancer were matched with 37,496 control participants for sex, age, income, and region of residence.

Figure 2

Subgroup analyses of PPI users (non-user [ref] vs. user) for colorectal cancer according to (a) age, sex, income, and region of residence and (b) CCI score, prescription dates of H2-blockers, and the number of GERD treatments visualized on a forest plot. Abbreviations: PPI, proton pump inhibitor; CCI, Charlson Comorbidity Index.

Figure 3

Subgroup analyses of PPI duration (non-user (ref) vs. ≥1 day and <30 days, ≥30 days and < 90 days, and ≥90 days PPI prescription dates) for colorectal cancer according to (a) age, sex, income, and region of residence and (b) CCI score, prescription dates of H2-blockers, and number of GERD treatments visualized on forest plots. Abbreviations: PPI, proton pump inhibitor; CCI, Charlson Comorbidity Index.

Figure 3

Subgroup analyses of PPI duration (non-user (ref) vs. ≥1 day and <30 days, ≥30 days and < 90 days, and ≥90 days PPI prescription dates) for colorectal cancer according to (a) age, sex, income, and region of residence and (b) CCI score, prescription dates of H2-blockers, and number of GERD treatments visualized on forest plots. Abbreviations: PPI, proton pump inhibitor; CCI, Charlson Comorbidity Index.