Chronic Proton Pump Inhibitor Therapy and the Risk of Colorectal Cancer

Background & Aims: Chronic acid suppression by proton pump inhibitor therapy can lead to hypergastrinemia. Because existing evidence suggested an association between hypergastrinemia and colorectal cancer, we examined whether long-term proton pump inhibitor use is associated with an increased risk of colorectal cancer in a population-representative cohort. Methods: We conducted a nested case-control study among patients 50 years of age and older and with ≥5 years of colorectal cancer-free initial follow-up in the General Practice Research Database (1987-2002) from the United Kingdom. Cases consisted of all patients with an incident diagnosis of colorectal cancer. Using incidence density sampling, up to 10 controls were matched with each case on practice site and both duration and calendar time of follow-up before the index date. The primary exposure of interest was ≥5 years of cumulative proton pump inhibitor therapy. We assessed the presence of duration-response and dose-response effects. Results: We identified 4432 incident colorectal cancer cases and 44,292 controls. The adjusted odds ratio for ≥5 years of proton pump inhibitor exposure was 1.1 (95% confidence interval, 0.7-1.9). Among high-dose proton pump inhibitor users (ie, ≥1.5 defined daily doses/day), there was a nonstatistically significant trend toward an increased risk with increasing duration of use (test for trend, P = .2). However, patients with pernicious anemia were not at increased risk for colorectal cancer (adjusted odds ratio, 0.9; 95% confidence interval, 0.6-1.3). Conclusions: Long-term proton pump inhibitor therapy at a regular dose is not associated with a significantly increased risk of colorectal cancer.