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How Statins May Increase Prostate Cancer

Fountain Medical Court, Bonita Springs, Florida

Luca Mascitelli

Comando Brigata Alpina "Julia," Servizio Sanitario, Udine, Italy

Francesca Pezzetta

Cardiology Service, Ospedale di San Vito al Tagliamento, San Vito al Tagliamento, Italy

To the Editors: We read Dr. Platz's excellent editorial on statins in the prevention of prostate cancer, and we agree with her conclusion that it is premature to recommend statins for the prevention of advanced prostate cancer (1). However, there are recent data suggesting that statins may actually increase prostate cancer and also impair prostate cancer immunotherapy.

Long-term follow-up of the West of Scotland Coronary Prevention Study, a primary prevention trial involving middle aged men, showed a significant increase in prostate cancer among those men randomized to pravastatin compared with placebo (2). This is biologically plausible.

Interestingly, statins have been found to increase the number of CD4⁺CD25⁺ regulatory T cells (Treg) in vivo by inducing the transcription factor forkhead box P3 (3). Tregs impair host antitumor response by suppressing tumor-specific T-cell responses, which leads to increased cancer risk (4).

Indeed, Tregs have been reported to be increased in prostate cancer tissue compared with normal prostate tissue from the same prostate, and the concentration of Tregs in peripheral blood has been found to be higher in prostate cancer patients than in normal donors (5). Furthermore, a statin-induced increase in Tregs, favoring tumor escape, may exert a detrimental effect during cancer immunotherapy (6).

Therefore, there are data suggesting that statins may increase prostate cancer risk by increasing the concentration of Tregs. This needs our attention, given the widespread and increasing use of statins at higher doses in segments of the population already at risk for prostate cancer.

	References

Top References

 

1. Platz EA. Epidemiologic musing on statin drugs in the prevention of advanced prostate cancer. Cancer Epidemiol Biomarkers Prev 2007;16:2175–80.[Free Full Text]
2. West of Scotland Coronary Prevention-Study Group. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007;357:1477–86.[Abstract/Free Full Text]
3. Mausner-Fainberg K, Luboshits G, Mor A, et al. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4⁺CD25⁺ T cells. Atherosclerosis. Epub 2007 Sept 10.
4. Yakirevich E, Resnick MB. Regulatory T lymphocytes: pivotal components of the host antitumor response. J Clin Oncol 2007;25:2506–8.[Free Full Text]
5. Miller AM, Lundberg K, Ozenci V, et al. CD4⁺CD25 high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 2006;177:7398–405.[Abstract/Free Full Text]
6. O'Mahony D, Morris JC, Quinn C, et al. A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin Cancer Res 2007;13:958–64.[Abstract/Free Full Text]

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