Proton pump inhibitor use and risk of colorectal cancer: a population-based, case-control study.
OBJECTIVE
Use of proton pump inhibitors (PPIs) has been associated with elevated levels of serum gastrin. Because hypergastrinemia increases colorectal mucosa proliferation and has been associated with risk of colorectal cancer (CRC) in human beings, we conducted a large population-based study in Denmark to assess whether PPI use is associated with CRC risk.


METHODS
We conducted the study in North Jutland County, Denmark. From the County Hospital Discharge Registry we identified incident cases of CRC during the period 1989-2005. Using risk set sampling we selected approximately 10 controls from the Danish Civil Registration System, with matching for sex and birth year. PPI use was ascertained in the Prescription Database of North Jutland (and so recorded before CRC diagnosis) and analyzed with conditional logistic regression adjusted for multiple covariates.


RESULTS
We identified 5589 cases of CRC which were compared with 55,890 controls. In a comparison of ever to never or rare users (< or =30 pills during observation period), no evidence was observed of increased risk (adjusted odds ratio [OR], 1.11; 95% confidence interval [CI], 0.97-1.27). When we compared the most intense users of PPI (more than every other day) with never or rare users, we found that no increased cancer risk was shown in either short-term users (adjusted OR, 1.07; 95% CI, 0.86-1.34) or long-term users (>7 years; adjusted OR = 1.09; 95% CI, 0.58-2.06).


CONCLUSIONS
The use of PPIs in clinical practice does not measurably increase the risk of CRC.
Robertson
Douglas J
DJ
VA Medical Center, White River Junction, VT 05009, USA. Douglas.robertson@med.va.gov
Larsson
Heidi
H
Friis
Søren
S
Pedersen
Lars
L
Baron
John A
JA
Sørensen
Henrik T
HT
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005755:Gastrins / Q000097:blood; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000473:pathology; D016015:Logistic Models; D008297:Male; D054328:Proton Pump Inhibitors; D012307:Risk Factors; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005755:Gastrins; D006635:Histamine H2 Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D054328:Proton Pump Inhibitors; D001241:Aspirin