title: Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis.
abstract: OBJECTIVE
  Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population.
  
  
  METHODS
  We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications.
  
  
  RESULTS
  In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98).
  
  
  CONCLUSIONS
  In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.
authors: Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom. Electronic address: Leo.Alexandre@uea.ac.uk.
authors: Leo
authors: L
authors: Alexandre
authors: Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Allan B
authors: AB
authors: Clark
authors: Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom.
authors: Hina Y
authors: HY
authors: Bhutta
authors: Roundwell Medical Centre, Norwich, United Kingdom.
authors: Sean
authors: S
authors: Holt
authors: Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom.
authors: Michael P N
authors: MP
authors: Lewis
authors: Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, United Kingdom.
authors: Andrew R
authors: AR
authors: Hart
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000517:prevention & control*; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000453:epidemiology / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D016588:Anticarcinogenic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Esophagus; HMG-CoA; Squamous Cell Carcinoma; Tumor