Meta-Analysis
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World J Gastroenterol. Feb 21, 2014; 20(7): 1858-1870
Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1858
Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies
Theodore Lytras, Georgios Nikolopoulos, Stefanos Bonovas
Theodore Lytras, Department of Occupational and Industrial Hygiene, National School of Public Health, 11521 Athens, Greece
Georgios Nikolopoulos, National Development and Research Institutes, Inc., New York, NY 10010, United States
Georgios Nikolopoulos, Hellenic Centre for Disease Control and Prevention, 15123 Athens, Greece
Stefanos Bonovas, Department of Pharmacology, School of Medicine, University of Athens, 11527 Athens, Greece
Stefanos Bonovas, Laboratory of Drug Regulatory Policies, IRCCS Mario Negri Institute for Pharmacological Research, 20156 Milan, Italy
Author contributions: Lytras T and Bonovas S designed the research; Lytras T and Bonovas S collected the data; Lytras T, Nikolopoulos G and Bonovas S analyzed and interpreted the data; Lytras T drafted the article; Lytras T, Nikolopoulos G and Bonovas S critically revised the article for important intellectual content and gave approval to be published; Bonovas S supervised the study.
Correspondence to: Theodore Lytras, MD, MPH, Department of Occupational and Industrial Hygiene, National School of Public Health, 196 Alexandras Ave., 11521 Athens, Greece. thlytras@gmail.com
Telephone: +30-694-6814271 Fax: +30-210-6412059
Received: September 30, 2013
Revised: November 13, 2013
Accepted: January 6, 2014
Published online: February 21, 2014
Processing time: 173 Days and 14.4 Hours
Abstract

AIM: To investigate the association between statin use and colorectal cancer risk, we conducted an updated meta-analysis of published studies.

METHODS: We performed a comprehensive search for studies published up to July 2013. Eligible studies for this meta-analysis were either randomized controlled trials (RCTs) or observational studies (case-control or cohort) evaluating any exposure to statins and the risk of colorectal cancer. Two reviewers selected studies based on predefined inclusion criteria, and abstracted the data. Pooled relative risk (RR) estimates with their 95%CI were calculated using fixed- and random-effects models. Then, we assessed the potential presence of publication bias and between-studies heterogeneity. To evaluate the results, we also performed a “leave-one-out” sensitivity analysis.

RESULTS: A total of 40 studies, involving more than eight million subjects, contributed to the analysis. They were grouped on the basis of study design and, consequently, three separate meta-analyses were conducted. A similar modest reduction in the risk of colorectal cancer with statin use was observed, which was not statistically significant among RCTs (RR = 0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR = 0.92, 95%CI: 0.87-0.98; n = 19). While we did not find significant evidence of selective outcome reporting or publication bias, substantial heterogeneity was detected, mainly among the observational studies. The sensitivity analysis confirmed the stability of our results.

CONCLUSION: A modest reduction in risk of colorectal cancer among statin users cannot be disproved. Further targeted research is warranted.

Keywords: 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors; Statins; Colorectal cancer; Systematic review; Meta-analysis; Cancer chemoprevention

Core tip: To investigate the association between statin use and colorectal cancer risk, we conducted a systematic review and meta-analysis of published studies. A total of 40 studies, involving more than eight million subjects, contributed to our analysis. A modest reduction in the risk of colorectal cancer with statin use was observed, which was not statistically significant among RCTs (RR = 0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR = 0.92, 95%CI: 0.87-0.98; n = 19). Further targeted research is warranted.