Journal of the National Cancer Institute Advance Access originally published online on June 24, 2008
JNCI Journal of the National Cancer Institute 2008 100(13):973-974; doi:10.1093/jnci/djn161
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Published by Oxford University Press 2008.
CORRESPONDENCE |
Response: Re: The Association Between Statins and Cancer Incidence in a Veterans Population
Affiliations of authors: Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA (WRF, EVL, RAL, MTB, LDF, JMG); Division of Aging (WRF, RES, EVL, JMG) and Cardiovascular Division and Division of Preventive Medicine (JMG), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Department of Epidemiology (EVL) and Department of Biostatistics (RAL), Boston University School of Public Health, Boston, MA; Department of Medicine, Boston University School of Medicine, Boston, MA (MTB, LDF)
Correspondence to: Wildon R. Farwell, MD MPH, Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston Division (151 MAV), 150 S Huntington Ave, Boston, MA 02130 (e-mail: wildon.farwell{at}va.gov).
We thank Drs Platz and Ravnskov for their interest in our paper. Dr Platz raises the issue of detection bias with respect to prostate cancer. We agree with Dr Platz that detection bias is a potential limitation of many observational studies that use administrative and electronic clinical datasets. We attempted to reduce detection bias in our study by restricting our study population to patients who made visits to a health-care provider on a routine basis and by restricting our comparison to patients taking statin vs patients taking antihypertensive medications. These restrictions resulted in analyses among patients with similar access to health care. Unfortunately, we do not have data at the present time that will allow us to describe the stage at diagnosis of prostate or other forms of cancer in our dataset.
Dr Ravnskov raises concern that statins may increase general carcinogenicity. He appears to combine results from the Scandanavian Simvastatin Survival Study (1) and the Heart Protection Study (HPS) (2) to infer that a statistically significant relationship may exist between statin use and increased risk for nonmelanoma skin cancer. We used the traditional definition of total cancer as all cancer excluding nonmelanoma because of historical precedent and the imprecision that is inherent in identifying noninvasive cancer through administrative codes alone. We agree that further investigation should examine the relationship between statins and nonmelanoma skin cancer. However, one should take care when combining unverified outcomes from different studies. In several of the studies (3,4,5) that Dr Ravnskov refers to as indicating a potential increased risk of cancer among statin users, pravastatin is either the study medication examined in the trial or the primary statin observed among the case and control subjects. Studies (6) have suggested a difference in the potential anticarcinogenic effect of statins on the basis of their lipophilic nature, with less lipophilic statins such as pravastatin having less potential anticarcinogenic effect. It is important to remember that all-cause mortality in the HPS was statistically significantly reduced among patients taking simvastatin compared with placebo, and other studies have established the general safety of statins, including pravastatin (7).
Dr Ravnskov also expressed concern that we may have failed to account for the relationship between serum cholesterol and cancer. We agree with Dr Ravnskov that previous observational studies have found a relationship between levels of serum cholesterol and future risk of cancer incidence. This is one reason why we included serum cholesterol in our multivariable-adjusted model of statins and cancer incidence. As we stated in our paper, adjustment for serum cholesterol did not statistically significantly impact the relationship between statins and cancer incidence in our multivariable-adjusted model. We are currently performing analyses to examine the relationship between cholesterol and cancer in our dataset and how this relationship may be affected by statins.
REFERENCES
1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandanavian Simvastatin Survival Study (4S). Lancet. (1994) 344(8934):1383–1389.
2. Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. (2002) 360(9326):7–22.
3. Iwata H, Matsuo K, Hara S, et al. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies. Cancer Sci. (2006) 97(2):133–138.
4. Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. (1996) 335(14):1001–1009.
5. Shepherd J, Blauw GJ, Murphy MB, et al. PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. Lancet. (2002) 360(9346):1623–1630.
6. Sivaprasad U, Abbas T, Durra A. Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer cells. Mol Cancer Ther. (2006) 5(1):2310–2316.
7. Pfeffer MA, Keech A, Sacks FM, et al. Safety and tolerability of pravastatin in long-term clinical trials: prospective pravastatin pooling (PPP) project. Circulation. (2002) 105(20):2341–2346.
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Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 972.
J Natl Cancer Inst 2008 100: 972-973.
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