Proton-pump inhibitor exposure and prevalence of colorectal adenoma: a retrospective analysis from the Sakkopi study

OBJECTIVE: Proton-pump inhibitors (PPIs) are among the most widely prescribed long-term medications worldwide, yet concerns remain about their potential role in colorectal carcinogenesis. Experimental data suggest that PPI-induced hypergastrinaemia may promote colonic epithelial proliferation, but epidemiological findings are inconsistent, and colonoscopy-based evidence is limited. METHODS: We studied 4476 asymptomatic adults who underwent structured screening colonoscopy in Austria between 2007 and 2020 as part of the Sakkopi study. Regular PPI use, including dose stratification, was evaluated in this retrospective analysis in relation to adenoma prevalence, burden and anatomical distribution. Multivariable logistic regression was adjusted for age, sex, metabolic syndrome, smoking status and family history of colorectal cancer. Multinomial models examined non-advanced and advanced adenomas separately. RESULTS: A total of 322 (7.2%) participants reported regular PPI use. Compared with non-users, PPI users were older, had higher body mass index and more frequently fulfilled metabolic syndrome criteria. Adenomas were detected in 39% of PPI users and 33% of non-users (p=0.032). In adjusted analyses, PPI use was not associated with adenoma presence (OR 1.05; 95% CI 0.83 to 1.35), number or distribution. Dose stratification showed no gradient effect: adjusted ORs were 0.85 (0.58 to 1.26) for half-dose and 1.19 (0.83 to 1.7) for standard-dose therapy. Multinomial analyses yielded consistent null results for both non-advanced and advanced adenomas in adjusted analysis. CONCLUSION: In this large and well-characterised screening cohort, regular PPI therapy was not associated with colorectal adenoma prevalence, irrespective of dose or lesion characteristics.