title: Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk.
abstract: BACKGROUND
  Laboratory data suggest a role of angiotensin II in the pathogenesis of colorectal cancer (CRC). Whether angiotensin converting enzyme inhibitor (ACE-I) and/or angiotensin receptor blocker (ARB) use reduces the risk of colorectal neoplasia remains unclear. Given their widespread use, we sought to determine whether exposure to these agents would have a secondary benefit on CRC incidence.
  
  
  METHODS
  A nested case-control study was conducted using EPIC's General Practice Research Database (1987-2002). The study cohort consisted of hypertensive patients. Case patients were those diagnosed with CRC after the diagnosis of hypertension. Each case patient was matched to up to 10 control subjects on age, sex, and both calendar year and duration of follow-up using incidence density sampling. The association between CRC and ACE-I/ARB exposure was assessed with conditional logistic regression. All statistical tests were two-sided.
  
  
  RESULTS
  Two thousand eight-hundred forty-seven case patients were matched with 28239 control subjects. The adjusted odds ratios (ORs) of CRC were 0.84 (95% confidence interval [CI] = 0.72 to 0.98; P = .03) for or more years of ACE-I/ARB therapy and 0.75 (95% CI = 0.58 to 0.97; P = .03) for 5 or more years of exposure. The strength of this association increased with high-dose exposure (OR = 0.53; 95% CI = 0.35 to 0.79; P = .003 for ≥3 years of high-dose exposure). Among patients receiving antihypertensive medications, the association with long-term therapy was no longer statistically significant for ≥5 years), but the benefit of high-dose therapy remained (OR = 0.59; 95% CI = 0.39 to 0.89; P = .01 for ≥3 years of high-dose exposure).
  
  
  CONCLUSIONS
  Long-term/high dose exposure to ACE-Is/ARBs may be associated with a decreased incidence of CRC.
authors.affiliation: Affiliations of authors: Division of Gastroenterology (GAM, Y-XY) and Center for Clinical Epidemiology and Biostatistics (GAM, JHH, Y-XY), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: George A
authors.initials: GA
authors.lastname: Makar
authors.forename: John H
authors.initials: JH
authors.lastname: Holmes
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D016208:Databases, Factual; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D016017:Odds Ratio; D020011:Protective Agents / Q000627:therapeutic use; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016588:Anticarcinogenic Agents; D000959:Antihypertensive Agents; D020011:Protective Agents