Can Statins Prevent Cancer?
What are statins?
Statins are a type of drug taken by millions of Americans to lower cholesterol. This class of drugs works by blocking an enzyme known as HMG-CoA (3-hydroxy-3-methyglutaryl COA) reductase, which the body needs to make cholesterol. Statins help to treat and prevent heart disease by lowering blood cholesterol. In the United States, statins are available by prescription only.
Animal research and ongoing observation of people who take statins suggest that these drugs may lower the risk of certain cancers, including colorectal and skin cancers. Statins' known benefits in preventing cardiovascular disease, along with years of strong evidence that these agents are relatively safe, have led researchers to explore whether statins have the potential to prevent cancer. People should not take statins for cancer prevention outside of a clinical trial.
By exploring the effects of statins on the process of cancer at the molecular level, researchers have found that statins work against critical cellular functions that may help control tumor initiation, tumor growth, and metastasis. Specifically, statins reduce (or block) the activity of the enzyme HMG-CoA reductase and thereby reduce the levels of mevalonate and its associated products. The mevalonate pathway plays a role in cell membrane integrity, cell signaling, protein synthesis, and cell cycle progression, all of which are potential areas of intervention to arrest the cancer process.
Although generally well-tolerated, statins have been associated with muscle pain (myopathy) and liver toxicity (hepatotoxicity). People who take statins should be monitored by their health care providers for these reasons.
NCI's Cancer Prevention Clinical Trials Consortia is developing a trial for people at increased risk for colorectal cancer who also have been found to have aberrant crypt foci (ACF). ACF are clusters of abnormal cells in the lining of the colon and rectum that have been associated with the development of colorectal tumors. Using existing technology, ACF represent the earliest stage of detectable risk for colorectal cancer.
Studies have shown that statins inhibit the growth of colon cancer cells grown in the laboratory. Consistent preventive effects of certain statins against colon cancer were first described in cancer studies in rodents published in 1994.
Some human observational studies have since suggested that statins may have protective effects against colorectal cancer. Most recently, researchers from the University of Michigan, collaborating with researchers in Israel, compared the use of statins among 1,953 patients who were diagnosed with colorectal cancer and 2,015 other people who did not have the disease. This study specifically associated a 47 percent reduction in the risk of colorectal cancer with statin use (as opposed to the use of another type of lipid-lowering drug, fibrates).
NCI is developing a phase II placebo-controlled trial to evaluate whether lovastatin can reverse pre cancerous changes in atypical (so-called dysplastic) nevi, a precursor to melanoma skin cancer, and thus have the potential to prevent progression to melanoma. Ken Linden, M.D., Ph.D., a researcher in dermatology at the University of California, Irvine, will be leading this multi center effort. The study will begin patient enrollment in late 2005 or early 2006.
Two large cardiovascular clinical trials have demonstrated a significant reduction in skin cancer among patients taking lipid-lowering drugs. Although clinical data do not consistently show a decreased risk of skin cancer with statin use, various human trials and pre clinical studies suggest that statins may have chemo preventive activity against skin cancer.
For more information about cancer, visit the NCI Web site at https://www.cancer.gov or call NCI's Cancer Information Service at 1–800–422–6237.
Information on cancer prevention is available at the NCI Division of Cancer Prevention Web site at prevention.cancer.gov on the-web.
More information on cholesterol-lowering drugs can be obtained from the FDA website at www.fda.gov.