Statins and cancer

I have written here before about "inferential" research results—results that are derived from studies that were actually studying something else, and low and behold, an unexpected result emerged. Scientifically we describe these provocative findings as "hypothesis generating," meaning results that are worthy of more detailed investigations.

These are just the kind of results that show that one of the most widely prescribed drug class, statins—drugs that are designed for lowering cholesterol—may also have a positive effect in decreasing several common cancers.

As with all pharmaceuticals, statins do have some potentially significant side effects, and thus their use should be carefully monitored.

Here's a recent article from the Harvard Men's Health Watch that covers what we know about statins' possible cancer-fighting effect. 

Might statins actually reduce the risk of cancer? This hope is based mainly on results from a large series of laboratory experiments, which, taken together, are interesting, even hopeful. But it's a long way from the lab to the clinic, and it will be years before we know if these basic experiments translate into practical benefits. Indeed, neither a 2006 meta-analysis of 26 statin trials nor the three large studies cited above to support the safety of statins found any protective effect against cancer. But the trials were designed principally to study heart disease, and they were relatively brief, especially compared to the many years it takes for most cancers to develop and grow.

While the results are mixed, some clinical observations do suggest benefit. For example, a Canadian study of 6,721 people 65 years of age and older linked statin use to a 28% decline in the risk of cancer. In a 2004 study of 3,129 patients with cancer and 16,976 people without the disease, statin use for four years or longer was linked to a 20% reduction in the incidence of malignancy.

All the reports cited thus far evaluated overall cancer risk, but several smaller studies have investigated individual malignancies, with mixed results. Researchers have reported no benefit for breast cancer and melanoma, but a 2007 study linked statins to a reduced risk of lung cancer. Most of the attention, though, has focused on colon and prostate cancer.

A 2005 report in the New England Journal of Medicine provides one of the most optimistic views of statins and cancer. Scientists in Israel compared 1,953 colon cancer patients with 2,015 healthy individuals. In addition to evaluating the impact of statin therapy, they carefully considered other factors that might affect the disease, including ethnicity, family history, physical activity, use of aspirin and other nonsteroidal anti-inflammatory drugs, vegetable and red meat consumption, and blood cholesterol levels. Even after considering all these factors, statin use was linked to a 47% reduction in the likelihood of colon cancer.

While this study raised the hope that statins might reduce the risk of colon cancer, a 2006 report was pessimistic. Researchers at the American Cancer Society have been tracking 132,136 men and women as part of the Cancer Prevention Study II Nutrition Cohort. Between 1997 and 2001, 815 of these subjects developed colon cancer. People taking cholesterol-lowering drugs were just as vulnerable as those not taking them. Unlike the encouraging Israeli study, however, this study lumped all cholesterol-lowering drugs together rather than focusing on the statins themselves. Three 2007 American studies did specifically evaluate statins and colon cancer. Although the use of statins was not associated with overall protection, in one study it was linked to a 51% decrease in the risk of advanced Stage IV disease. More research is needed, and since colon cancer is the fourth most commonly diagnosed internal malignancy in the United States, it's sure to follow.

Like colon cancer cells, prostate cancers are inhibited by statins in laboratory experiments. Clinical results have been mixed, but the latest studies are hopeful.

In February 2003, the disappointing result of a study found no benefit for statin use in a comparison of 1,009 men with prostate cancer and 1,387 men who were healthy. But two newer reports are considerably more optimistic. A 2005 Oregon study of 302 veterans with an average age of 65 reported that statin use was associated with a 62% reduction in the diagnosis of prostate cancer and a 76% reduction in aggressive prostate cancers. A much larger 2006 Harvard study of 34,989 men linked statin use with a 49% lower risk of advanced prostate cancer and a 61% lower risk of metastatic or fatal disease. The greatest protection was observed in the men who had been taking a statin drug the longest.

How might statins protect against prostate cancer? In addition to the general mechanism discussed earlier, there are some interesting possibilities specific to the prostate. For one thing, Harvard scientists report that high cholesterol levels can fuel the growth of prostate cancers in mice. In men, statin therapy appears to reduce blood PSA levels; the decline is greatest among men with the largest reduction in cholesterol levels. And a 2007 study found that statin therapy boosts levels of vitamin D in humans; in turn, vitamin D may help reduce the risk of prostate cancer.

The bottom line

Taking a statin to prevent cancer doesn't make sense—yet. Hints and hopes are not enough; until proof is available, doctors should not prescribe a statin simply to reduce the risk of any of these conditions. Still, patients who need a statin for cardiovascular protection may be heartened by the hope that cancer prevention may be a "side effect" of these important medications.

What's your take on statins' effects on cancer risk?

Marc Garnick, M.D., is an internationally renowned expert in medical oncology and urologic cancer, with a special emphasis on prostate cancer. He is a Clinical Professor of Medicine at Harvard Medical School and maintains an active oncology practice at Beth Israel Deaconess Medical Center. Dr. Garnick serves as Editor in Chief of Perspectives on Prostate Diseases, a quarterly report from Harvard Health Publications.

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