Abstract
PurposeDespite plausible mechanisms, the clinical significance of long-term proton pump inhibitor (PPI) use to colorectal cancer (CRC) remains unknown. The purpose of this study was to investigate the association between PPI use and CRC development.MethodsWe conducted a population-based prospective cohort study using the Korean nationwide claims database merged with national health examination data. The study cohort included a total of 451,284 participants who were tracked to identify cases of CRC since 2007. We assessed and standardized PPI use before the index date using the Defined Daily Dose system. We calculated the hazard ratios and their 95% confidence intervals to assess the association between PPI use and CRC occurrence using Cox proportional hazard regression models with adjustment for potential confounders. We performed subgroup analyses of the effect of PPI exposure on CRC development stratified by the CRC risk.ResultsThere were 5,304 cases of CRC during the study period of 2,908,152 person-years. PPI use was not associated with CRC risk overall. The incidence of CRC was higher among individuals who were elderly, male, more obese, and drank alcohol more frequently and among those who had more comorbidities. Further subgroup analyses revealed that the hazard effect of PPI use increased linearly in a dose-dependent manner with the number of CRC risk factors for which the risk level was considered low.ConclusionWithin the low-risk population, PPI use was associated with an increased risk of CRC, although the association did not weigh the effects of conventional risk factors.
Highlights
Proton pump inhibitor (PPI) is the mainstay treatment for acid-related diseases such as peptic ulcer disease and gastroesophageal reflux disease [1]
PPI use was not associated with colorectal cancer (CRC) risk overall
Further subgroup analyses revealed that the hazard effect of PPI use increased linearly in a dose-dependent manner with the number of CRC risk factors for which the risk level was considered low
Summary
Proton pump inhibitor (PPI) is the mainstay treatment for acid-related diseases such as peptic ulcer disease and gastroesophageal reflux disease [1]. For most indications PPI should only be used for 4–8 weeks, many patients require long-term use [2]. There are concerns about the safety of longterm PPI use, with increasing concern for a possible association with the risk of gastrointestinal cancers including colorectal cancer (CRC) [3, 4]. CRC has long been considered a Western disease, but the incidence of CRC has been steeply increasing in the Asia-Pacific region during past decades [5]. Korea had the highest age-standardized incidence worldwide (45.0 per 100,000 individuals) according to the GLOBOCAN 2012 because of an exponential increase in obesity and a decrease in physical activity, which result from a Westernized lifestyle accompanied by a marked increase in the consumption of calorie-rich diets [6]. Efforts to control risk factors as well as to detect CRC earlier are of substantial importance
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