The recent study published in the December 2011 issue of Prostate, suggesting that the use of statins may actually increase a man’s risk of prostate cancer, runs contrary to others published studies that showed a relationship between the use of cholesterol-lowering drugs and a decreased incidence of prostate cancer. This new data underscores the need for additional research to further understand the role of statins in either lowering or increasing the risk of cancer. Patients should consult with their physicians to assess their personal use of statins based on their specific health history.

You can read the article here.

PCF asked two research professionals to weigh in on the topic: Lorelei Mucci, ScD (a PCF Young Investigator-2008), at the Harvard School of Public Health, and Michael Freeman, PhD, at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles. Please read their responses below.

An Update on Cholesterol and Prostate Cancer

Michael R. Freeman, PhD
Samuel Oschin Comprehensive Cancer
Cedars-Sinai Medical Center
Los Angeles

Cholesterol is a fatty component of normal cell membranes and a precursor of a variety of important hormones, including androgens. The prostate normally synthesizes cholesterol at a high rate, and the aging prostate suffers defects in cholesterol metabolism, leading to accumulation of cholesterol deposits. As a result of its role in the control of cell membrane structure, cholesterol indirectly affects biochemical signals that regulate cell growth and survival. Cholesterol-rich membrane microdomains have been identified as important in regulating biochemical pathways known to be used by prostate cancer cells during disease progression.

There is now considerable evidence that both circulating cholesterol and cholesterol present in prostate cancer cells is a factor in progression to advanced disease. Over the past 5 years, the majority of adequately powered epidemiological studies have found an inverse association between the use of cholesterol-lowering drugs (primarily statins) and aggressive prostate cancer, suggesting that long-term cholesterol-lowering therapy is chemopreventive against lethal disease. Consistent with this literature, high circulating cholesterol has now been shown to be positively associated with advanced disease, suggesting that high cholesterol may be tumor-promoting. Studies in mice have shown that experimentally elevated cholesterol promotes the growth of prostate tumors, while cholesterol suppression retards tumor growth. Finally, recently published data show that high cholesterol can result in higher levels of androgens in prostate tumor cells, even with normal levels of androgen in the blood (i.e., in the absence of hormonal suppression). This last observation suggests that circulating cholesterol is a source of tumor androgen in castration-resistant disease.

These findings, from a wide range of human and animal studies, support further investigation into the details of cholesterol metabolism, and options on cholesterol management and targeting, in understanding, preventing and treating prostate cancer. 

 

Statins and Prostate Cancer Risk

Lorelei Mucci, ScD
Dana-Farber/Harvard Cancer Center
Harvard School of Public Health
Boston

In epidemiological research, there are two main approaches to examining associations between exposure and disease risk: cohort and case-control studies.  A well-designed case-control study is an efficient and valid epidemiological alternate to a cohort study, in which the controls are meant to serve as a proxy of the frequency of exposure in the study base from where the cases come. However, the case-control design is susceptible to potential biases distinct from cohort studies that may induce spurious associations.

In the December issue of Prostate, Chang et al examine the association between use of statins and the risk of prostate cancer in a case-control study within the National Health Insurance Program of Taiwan.  Cases include men diagnosed with prostate cancer within this registry between 2005 and 2008.  The proper selection of the control group should have been a sampling of the person-time experience of the NHI database over this same time period in order to accurately reflect the prevalence of statin use in the study base.  A concern is that the sampling of the controls, whereby the authors restricted the sampling to men with certain conditions that were thought to be unrelated to the exposure.  However, the association between statin use and these outcomes is unknown, and thus the controls may have a frequency of statin use that is higher or lower than the true study base and thus have induced a selection bias.  Two additional considerations in interpreting the findings from Chang et al are 1-) the small number of cases in the “exposed” categories and 2-) the lack of data on tumor stage and grade.  Taken together, one must caution against assuming the observed positive association between statin use and prostate cancer is a causal association.

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