Statins and cancer

A number of studies are attempting to answer the question: Might statins actually reduce the risk of cancer?
Statins and cancer
By Harvard Medical International
Wed 12 Dec 2007 05:46 PM

The first statin drug was approved for clinical use in the United States in 1987. Doctors quickly recognized that lovastatin (Mevacor) had an excellent effect on blood cholesterol levels, but they worried about possible side effects. In the next 20 years, the statin family grew to its current roster of six drugs. A seventh, cerivastatin (Baycol), was withdrawn because of muscle toxicity, but the others have proved safe - and they've shown an unrivalled ability to reduce LDL ("bad") cholesterol levels and cut the risk of heart attacks and cardiovascular deaths.

Some results suggest that statins may strengthen the effects of standard cancer drugs or radiation.

Since statins are the largest-selling prescription drugs in this country, doctors have wondered if they may have benefits beyond the heart. Indeed, statins produce a substantial reduction in the risk of stroke. And although the results are less conclusive, statins are being studied for possible benefits against a variety of diseases, from cataracts and dementia to chronic lung disease, osteoporosis, and the flu. And now attention is turning to statins and cancer.

Not to worry

In the early days, some scientists worried that statins might protect the heart at the cost of an increased risk of cancer. Their concern was based on experiments showing that several types of lipid-lowering drugs, including statins, appeared to increase the occurrence of malignancies in rodents. But men are not mice, and those fears have proved groundless. For example, the Heart Protection Study of more than 10,000 statin users and the Scandinavian Simvastatin Survival Study of more than 2,000 users found no increased cancer risk. More recently, a meta-analysis of 14 statin trials involving more than 90,000 individuals agreed that statins do not increase the risk of cancer.

Perhaps to hope

Statin safety is good news. But now that doctors have put worries about statins and cancer to rest, they are asking a radically different question: Might statins actually reduce the risk of cancer?

Their hope is based mainly on a large series of laboratory experiments. Although the details vary, the basic idea is to grow cancer cells in test tubes with or without a statin drug in the culture medium. Many labs from around the world have been involved, with different results. In general, though, scientists agree that statins are able to slow the growth of cells from human cases of prostate cancer, bladder cancer, breast cancer, and other malignancies. Several mechanisms have been identified.
Statins may reduce the activity of genes that turn cells cancerous and increase the activity of other genes that protect cells from turning cancerous. They may starve the blood supply to growing tumours. In addition, statins may reduce a cancer cell's ability to spread and may even encourage cancer cells to commit suicide (a process called apoptosis). Finally, some results suggest that statins may strengthen the effects of standard cancer drugs or radiation.

Statins are being studied for possible benefits against a variety of diseases.

Taken together, these results 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. 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. Similarly, a 2005 investigation of 334,754 Danes reported that statin users enjoyed a 14% lower risk of cancer than non-users. Moreover, the apparent benefit did not depend on cholesterol reduction per se, since statin users were 27% less likely to develop cancer than those who used other types of lipid-lowering drugs.

Cancer is not one disease but many. 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.

Coloncancer

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.

Prostate cancer

Men are more likely to develop prostate cancer than colon cancer, and a similar number of American men die from the two diseases each year. 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.

Statins for cancer?

Not yet. There are several good reasons for doctors to prescribe a statin drug. Most often it's a high LDL ("bad") cholesterol level, but it's also clear that patients with diabetes, heart disease, or other forms of atherosclerosis can benefit from statin therapy even if they start out with normal LDL levels. And if new trends continue, statin therapy may soon be extended to some vulnerable individuals with low LDL levels.

Cancer is another matter. As for cataracts, chronic lung disease, and dementia, there are hopeful hints that statin therapy may help. But 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. And even without a statin, men who reduce their consumption of saturated fat can expect a number of health benefits: lower cholesterol levels, reduced cardiac risk, and prostate protection.

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