Statins may reduce risk of advanced PCa by 50%


Anaheim, CA--Data from a very large, prospective cohort study suggest that men taking statin drugs may reduce their risk of advanced prostate cancer by more than half and reduce their risk of metastatic or fatal disease by more than two-thirds.

Interestingly, however, the use of statins, which are used commonly in the treatment of elevated cholesterol, was not associated with a reduction in risk of organ-confined prostate cancer, according to Elizabeth A. Platz, ScD, and colleagues.

Dr. Platz, assistant professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, cautioned that these data are not conclusive enough to warrant prescribing statins to reduce cancer risk alone, that confirmatory studies are needed, and that directed studies are needed to determine how pathways influenced by statins may account for the observed reduction in risk.

The men were asked on biennial questionnaires to report use of cholesterol-lowering drugs in the previous 2 years, and in 2000, they were asked to report specifically on use of statins. Statins accounted for 90.9% of the cholesterol-lowering drug use between 1998 and 2000.

Duration affects risk In a presentation here at the American Association for Cancer Research annual meeting, Dr. Platz said all subjects in her study were free of cancer diagnosis in 1990. When prostate cancer was reported on follow-up questionnaires, it was confirmed by a review of medical and pathology records.

There were 2,074 prostate cancer cases through January 2000, of which 283 were regionally invasive, metastatic, or fatal. Of those, 206 were metastatic or fatal.

Dr. Platz reported finding a hazard ratio for advanced prostate cancer of 0.54 for men who used cholesterol-lowering drugs, including statins, compared with nonusers.

The inverse association was even stronger for metastatic and fatal disease, with a hazard ratio of 0.34.

"There was also a trend toward further reduction of risk of advanced prostate cancer with increasing duration of statin use," Dr. Platz said.

However, there were no associations for these drugs with risk of any prostate cancer (a hazard ratio of 0.99) or risk of organ-confined disease (hazard ratio of 1.02).

Is lower cholesterol the answer? Besides lowering cholesterol by inhibiting HMG-coenzyme A reductase-the rate-limiting enzyme in cholesterol synthesis-statins also exhibit pro-apoptotic and anti-inflammatory activities, Dr. Platz said.

At a press conference here highlighting important presentations, Dr. Platz was asked about the possibility that simply lowering cholesterol might reduce risk of advanced cancer, rather than through more complicated pathways.

She said it is a possibility because cholesterol is over-represented in prostate cell membranes, and removing high levels of serum cholesterol might have some effect on cell survival. Cholesterol is a precursor for sex steroid hormones, she said.

Andrew Dannenberg, MD, director of cancer prevention, New York Presbyterian Hospital-Cornell, New York, and moderator of the press conference, called Dr. Platz's data extremely exciting.

"The potential use of statins as anticancer agents is appreciated, but this study stands apart based on its quality," he said. "The suggestion has been made that the statins do not impact on the incidence of prostate cancer, rather on the natural history of the disease, thereby leading to a better prognosis.

"It also underscores a growing theme in human disease; that is, the commonality of mechanism related to heart disease and cancer, with inflammation, for example, being shared by both."

Dr. Dannenberg noted that the National Cancer Institute, in a new phase-I/II consortium, is considering evaluation of statins as chemopreventive agents.

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