1. 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 available by prescription include atorvastatin (Lipitor^™), lovastatin (Mevacor^™), pravastatin (Pravachol™), and simvastatin (Zocor™). In the United States, statins are available by prescription only.

2. Can statins prevent cancer?

   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.

3. Why do scientists think statins might prevent cancer?

   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.

4. What are the common side effects of statins?

   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.

5. Is the National Cancer Institute (NCI) supporting research testing whether statins might prevent colorectal cancer?

   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.

   This NCI-sponsored phase II trial will begin patient enrollment in late 2005 or early 2006. The study will assess the efficacy of atorvastatin (and two other investigational agents, an anti-inflammatory, sulindac, and another compound that promotes the growth of healthy bacteria in the colon) against ACF. Paul Limburg, M.D., a researcher in gastroenterology at the Mayo Clinic (Rochester, Minn.), will be leading this multicenter effort.

6. What evidence is there that statins may have an effect on 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). [Statins and the risk of colorectal cancer. Poynter, JN., et al. New England Journal of Medicine, May 26, 2005, (352:2184–92].

7. Is NCI supporting research with statins to prevent other types of cancer?

   NCI is developing a phase II placebo-controlled trial to evaluate whether lovastatin can reverse precancerous 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 multicenter effort. The study will begin patient enrollment in late 2005 or early 2006.

8. What evidence is there that lipid-lowering drugs can prevent skin cancer?

   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 preclinical studies suggest that statins may have chemopreventive activity against skin cancer.

9. Where can I get more information?

   For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1–800–4–CANCER (1–800–422–6237).

   Information on cancer prevention is available at the NCI Division of Cancer Prevention Web site at http://prevention.cancer.gov on the Internet.

   More information on cholesterol-lowering drugs can be obtained from the FDA Web site at http://www.fda.gov on the Internet.

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Glossary Terms

Clusters of abnormal tube-like glands in the lining of the colon and rectum. Aberrant crypt foci form before colorectal polyps and are one of the earliest changes that can be seen in the colon that may lead to cancer. Also called ACF.

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

Clusters of abnormal tube-like glands in the lining of the colon and rectum. ACF form before colorectal polyps and are one of the earliest changes that can be seen in the colon that may lead to cancer. Also called aberrant crypt foci.

Having to do with reducing inflammation.

The active ingredient in a drug used to lower the amount of cholesterol in the blood and to prevent stroke, heart attack, and angina (chest pain). It is also being studied in the prevention and treatment of some types of cancer and other conditions. Atorvastatin blocks an enzyme that helps make cholesterol in the body. It also causes an increase in the breakdown of cholesterol. It is a type of HMG-CoA reductase inhibitor and a type of statin.

A large group of single-cell microorganisms. Some cause infections and disease in animals and humans. The singular of bacteria is bacterium.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Having to do with the heart and blood vessels.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

The process a cell goes through each time it divides. The cell cycle consists of a series of steps during which the chromosomes and other cell material double to make two copies. The cell then divides into two daughter cells, each receiving one copy of the doubled material. The cell cycle is complete when each daughter cell is surrounded by its own outer membrane. Also called mitotic cycle.

The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer.

A waxy, fat-like substance made in the liver, and found in the blood and in all cells of the body. Cholesterol is important for good health and is needed for making cell walls, tissues, hormones, vitamin D, and bile acid. Cholesterol also comes from eating foods taken from animals such as egg yolks, meat, and whole-milk dairy products. Too much cholesterol in the blood may build up in blood vessel walls, block blood flow to tissues and organs, and increase the risk of developing heart disease and stroke.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Having to do with the colon or the rectum.

In science, a substance that is made up of more than one ingredient.

The process of identifying a disease, such as cancer, from its signs and symptoms.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

A type of nevus (mole) that looks different from a common mole. A dysplastic nevus is often larger with borders that are not easy to see. Its color is usually uneven and can range from pink to dark brown. Parts of the mole may be raised above the skin surface. A dysplastic nevus may develop into malignant melanoma (a type of skin cancer).

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

A protein that speeds up chemical reactions in the body.

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The FDA also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called Food and Drug Administration.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

Fat.

A drug used to lower the amount of cholesterol in the blood and to prevent stroke, heart attack, and angina (chest pain). It is also being studied in the prevention and treatment of some types of cancer and other conditions. Lipitor blocks an enzyme that helps make cholesterol in the body. It also causes an increase in the breakdown of cholesterol. It is a type of HMG-CoA reductase inhibitor and a type of statin. Also called atorvastatin calcium.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

A drug used to lower the amount of cholesterol in the blood. It is also being studied in the prevention and treatment of some types of cancer. Lovastatin is a type of HMG-CoA reductase inhibitor (statin). Also called Mevacor.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

A very thin layer of tissue that covers a surface.

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).

A drug used to lower the amount of cholesterol in the blood. It is also being studied in the prevention and treatment of some types of cancer. Mevacor is a type of HMG-CoA reductase inhibitor (statin). Also called lovastatin.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

Refers to a clinical study in which the control patients receive a placebo.

A drug used to lower the amount of cholesterol in the blood and to prevent stroke and heart attack. It is also being studied in the treatment of cancer and other conditions. Pravachol blocks an enzyme that helps make cholesterol in the body. It may also make tumor cells more sensitive to anticancer drugs. It is a type of HMG-CoA reductase inhibitor, a type of statin, and a type of chemosensitizer. Also called pravastatin sodium.

The active ingredient in a drug used to lower the amount of cholesterol in the blood and to prevent stroke and heart attack. It is also being studied in the treatment of cancer and other conditions. Pravastatin blocks an enzyme that helps make cholesterol in the body. It may also make tumor cells more sensitive to anticancer drugs. It is a type of HMG-CoA reductase inhibitor, a type of statin, and a type of chemosensitizer.

A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

A doctor's order for medicine or another intervention.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

Cancer that forms in tissues of the skin. There are several types of skin cancer. Skin cancer that forms in melanocytes (skin cells that make pigment) is called melanoma. Skin cancer that forms in basal cells (small, round cells in the base of the outer layer of skin) is called basal cell carcinoma. Skin cancer that forms in squamous cells (flat cells that form the surface of the skin) is called squamous cell carcinoma. Skin cancer that forms in neuroendocrine cells (cells that release hormones in response to signals from the nervous system) is called neuroendocrine carcinoma of the skin. Most skin cancers form in older people on parts of the body exposed to the sun or in people who have weakened immune systems.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Any of a group of drugs that lower the amount of cholesterol and certain fats in the blood. Statins inhibit a key enzyme that helps make cholesterol. Statin drugs are being studied in the prevention and treatment of cancer.

A nonsteroidal anti-inflammatory drug (NSAID) that is being studied as a treatment for cancer.

The extent to which something is poisonous or harmful.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A process in which normal cells are changed so that they are able to form tumors. Substances that cause cancer can be tumor initiators.