Clinical–alimentary tractChronic Proton Pump Inhibitor Therapy and the 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
References (50)
- et al.
Who is using chronic acid suppression therapy and why?
Am J Gastroenterol
(2003) - et al.
Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis
Gastroenterology
(1990) - et al.
Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis
Gastroenterology
(1993) - et al.
Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice
Gastroenterology
(1997) - et al.
Gastrin-mediated effects of omeprazole on rat colon mucosa
Surgery
(1999) - et al.
Pentagastrin stimulates in vitro growth of normal and malignant human colon epithelial cells
Am J Surg
(1985) - et al.
Gastrin and colorectal cancer: a prospective study
Gastroenterology
(1998) - et al.
Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa
Gastroenterology
(2000) - et al.
Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients
Gastroenterology
(2004) - et al.
Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy
Gastroenterology
(1992)
Why are patients prescribed proton pump inhibitors?Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database
BMJ
The physiology of gastric acid secretion
N Engl J Med
Omeprazole in the long-term management of patients with acid-related diseases resistant to ranitidine
Scand J Gastroenterol Suppl
Serum gastrin levels during long-term omeprazole treatment
Aliment Pharmacol Ther
Relationship between reduction of gastric acid secretion and plasma gastrin concentration during omeprazole treatment
Scand J Gastroenterol
Role of gastrointestinal hormones in pancreatic cancer
J Hepatobiliary Pancreat Surg
Coexpression of gastrin and gastrin receptors (CCK-B and delta CCK-B) in gastrointestinal tumour cell lines
Gut
Characterization of cloned human cholecystokinin-B receptor as a gastrin receptor
Biochem Pharmacol
Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation
J Clin Invest
Processing and proliferative effects of human progastrin in transgenic mice
J Clin Invest
Hypergastrinemia promotes adenoma progression in the APC−/+ mouse model of familial adenomatous polyposis
Cancer Res
Growth-promoting effects of glycine-extended progastrin
Science
Incomplete processing of progastrin expressed by human colon cancer cells: role of noncarboxyamidated gastrins
Am J Physiol
The in vitro growth response of primary human colorectal and gastric cancer cells to gastrin
Int J Cancer
Elevated gastrin levels in patients with colon cancer or adenomatous polyps
Dig Dis Sci
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.