• 1/15/2008
  • web-based article
  • Wildon R. Farwell et al
  • JNCI Journal of the National Cancer Institute 2008 100(2):134-139

Background:
Meta-analyses of trials of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins for cardiovascular disease prevention have failed to show any statistically significant benefit of statins for cancer prevention. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence. We investigated this association in a population of veterans.

Methods:
We identified patients using antihypertensive medications but no cholesterol-lowering medications (n = 25594) and patients using statins (n = 37248) who were enrolled in the Veterans Affairs New England Healthcare System between January 1, 1997, and December 31, 2005. Age- and multivariable-adjusted Cox proportional hazards models were used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for cancer incidence, excluding nonmelanoma skin cancer, among patients taking statins compared with patients taking antihypertensive medications and among patients grouped by statin dose (as equivalent simvastatin dose). All statistical tests were two-sided.

Results:
The absolute incidence of total cancers was 9.4% among statin users and 13.2% among nonusers (difference = 3.8%, 95% CI = 3.3% to 4.3%, Pdifference < .001). Statin users had a statistically significant lower risk for total cancer than nonusers after adjustment for age (HR = 0.76, 95% CI = 0.73 to 0.80) and multiple potential confounders (HR = 0.74, 95% CI = 0.70 to 0.78). After multivariable adjustment, a statistically significantly decreased risk of all cancers was also associated with increasing statin use (Ptrend < .001).

Conclusions:
Patients using statins may be at lower risk for developing cancer. Additional observational studies and randomized trials of statins for cancer prevention are warranted.

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CONTEXT AND CAVEATS
Prior knowledge

In meta-analyses of trials of statins for cardiovascular disease prevention, statins failed to show any statistically significant cancer prevention activity. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence.

Study design

Retrospective cohort study of veterans using statin and veterans using antihypertensive medications (but not statins) who were enrolled in the Veterans Affairs health-care system. Information on the statins prescribed was available, and statin doses were converted to equivalent simvastatin doses.

Contribution

The absolute incidence of total cancer was 9.4% among statin users and 13.2% among nonusers. Statin users had a statistically significantly lower risk of total cancer than nonusers, after adjustment for age and multiple potential confounders. In a multivariable analysis, decreased risk of all cancers was statistically significantly associated with increasing statin doses.

Implications

Statin users may be at a lower risk for developing cancer. Additional observational and randomized studies investigating the relationship between statin use and the development of cancer are warranted.

Limitations

Patients may not have been first-time statin users. All new cancer diagnoses could not be verified. Quantitative information on smoking or alcohol exposure was not available. There were limited numbers of women and minorities in this cohort.

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The study sponsor had no role in the experimental design; the collection, analysis, or interpretation of the data; or in the writing and submission of the manuscript.

Authors:
Wildon R. Farwell, Richard E. Scranton, Elizabeth V. Lawler, Robert A. Lew, Mary T. Brophy, Louis D. Fiore, J. Michael Gaziano

Authors’ affiliations:
Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (WRF, EVL, RAL, MTB, LDF, JMG); Divisions of Aging (WRF, RES, EVL, JMG) and Preventive Medicine (JMG) and Cardiovascular Division (JMG), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Departments of Epidemiology (EVL), Biostatistics (RAL), and Medicine (MTB, LDF), Boston University School of Medicine, Boston, MA