Meta-Analysis
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World J Gastrointest Pharmacol Ther. Aug 6, 2013; 4(3): 69-79
Published online Aug 6, 2013. doi: 10.4292/wjgpt.v4.i3.69
Reduced esophageal cancer incidence in statin users, particularly with cyclo-oxygenase inhibition
Ian Leonard Phillip Beales, Abigail Hensley, Yoon Loke
Ian Leonard Phillip Beales, Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich NR4 7UY, United Kingdom
Abigail Hensley, Yoon Loke, Norwich Medical School, University of East Anglia, Norwich NR4 TJ, United Kingdom
Author contributions: Beales ILP and Loke Y jointly conceived the study; Beales ILP and Hensley A performed the searching and data extraction; Beales ILP wrote the initial and final versions of the paper and is guarantor of the paper; all authors performed the data analysis and have seen the raw data and agree with publication.
Correspondence to: Dr. Ian Leonard Phillip Beales, Clinical Senior Lecturer and Honorary Consultant Gastroenterologist, Department of Gastroenterology, Norfolk and Norwich University Hospital, Colney Ln, Norwich NR4 TJ, United Kingdom. i.beales@uea.ac.uk
Telephone: +44-1603-591003 Fax: +44-1603-593752
Received: April 16, 2013
Revised: May 22, 2013
Accepted: June 19, 2013
Published online: August 6, 2013
Abstract

AIM: To examine the association between statin use and the development of esophageal cancer

METHODS: We performed a systematic review and meta-analysis. Multiple databases (Pubmed, EMBASE, Cochrane Library, Web of Science, Wiley Interscience and Google Scholar) were systematically searched for studies reporting the association of statin use and the development of esophageal cancer. Literature searching and data abstraction were performed independently by two separate researchers. The quality of studies reviewed was evaluated using the Newcastle-Ottawa Quality assessment scale. Meta-analysis on the relationship between statin use and cancer incidence was performed. The effect of the combination of statin plus a cyclo-oxygenase inhibitor was also examined.

RESULTS: Eleven studies met eligibility criteria, 9 high and 2 medium quality. All were observational studies. Studies examining adenocarcinoma development in Barrett’s oesophagus included 317 cancers and 1999 controls, population-based studies examining all esophageal cancers included 371203 cancers and 6083150 controls. In the Barrett’s population the use of statins (OR = 0.57; 95%CI: 0.43-0.75) and cyclo-oxygenase inhibitors (OR = 0.59; 95%CI: 0.45-0.77) were independently associated with a reduced incidence of adenocarcinoma. Combined use of a statin plus cyclo-oxygenase inhibitor was associated with an even lower adenocarcinoma incidence (OR = 0.26; 95%CI: 0.1-0.68). There was more heterogeneity in the population-based studies but pooled adjusted data showed that statin use was associated with a lower incidence of all combined esophageal cancers (OR = 0.81; 95%CI: 0.75-0.88).

CONCLUSION: Statin use in patients with Barrett’s oesophagus is associated with a significantly lower incidence of adenocarcinoma. The chemopreventive actions of statins, especially combined with cyclo-oxygenase inhibitors deserve further exploration.

Keywords: Aspirin, Barrett’s oesophagus, Chemoprevention, Cancer risk, Esophageal carcinoma, Non-steroidal anti-inflammatory drugs, Statins

Core tip: Esophageal cancer remains a major burden upon health. The incidence of esophageal adenocarcinoma has increased dramatically in western countries. Experimental studies have suggested that statins may have useful actions against esophageal cancer cells. This systematic review and meta-analysis of observational studies shows that statin use was associated with a reduced incidence of all esophageal cancers (19% decrease). A more striking reduction in adenocarcinoma incidence in patients with Barrett’s esophagus taking statins was seen (43% decrease) and this effect was enhanced in those also taking cyclo-oxygenase inhibitors (74% decrease). This combination offers promise for chemoprevention and further interventional studies are warranted.