Gastroenterology

Gastroenterology

Volume 133, Issue 3, September 2007, Pages 748-754
Gastroenterology

Clinical–alimentary tract
Chronic Proton Pump Inhibitor Therapy and the Risk of Colorectal Cancer

https://doi.org/10.1053/j.gastro.2007.06.022Get rights and content

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.

Section snippets

Study Design

We conducted a nested case-control analysis in the General Practice Research Database (GPRD). This study was approved by the University of Pennsylvania Institutional Review Board and the GPRD Scientific and Ethical Advising Group.

Source of Data

The GPRD is a computerized medical record system of approximately 700 general practices in the United Kingdom.35 The database is broadly representative of the UK population in terms of sex, age, and geography.36 Under the National Health Services, 98% of the UK

Results

The response rate to the NSAID/aspirin survey was 56% among the PPI users and 58% among PPI nonusers. Overall, the most common reason for nonresponse was because the patient transferred out of the practice; other reasons were request being declined by physician or rarely by patient, as well as patient death. Among the responders, current long-term (ie, ≥180 days of total use within the year before the survey) NSAID/aspirin use was more common among the PPI users (39% vs 20%). Overall, 98% of

Discussion

In this large study in a population representative of the UK population, ≥5 years of PPI therapy was not associated with an increased risk of CRC. When analyzed by average daily dose, we did not observe a clinically important increase in the risk of CRC among long-term users receiving a regular dose on average. However, we could not completely exclude a risk increase among patients receiving high-dose PPI therapy for long durations.

Recent use of PPI therapy for <1 year was associated with a

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  • Cited by (0)

    Supported by a National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Mentored Career Development Award (K08 DK062978 to Y.-X.Y.). Y.-X.Y. has served as a consultant for AstraZeneca and has received grant support from AstraZeneca, Wyeth-Ayerst Laboratories, and GlaxoSmithKline. S.H. has served as a consultant for Wyeth-Ayerst Laboratories. J.D.L. has served as a consultant for Wyeth-Ayerst Laboratories. All other authors have no conflict of interest to disclose.

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