chemoprevention

n.
The use of chemical agents, drugs, or food supplements to prevent the development of cancer.

chemopreventive che'mo·pre·ven'tive adj. & n.

Key Terms: apoptosis, anti-inflammatory.

Definition

Chemoprevention is the attempt to prevent cancer from developing by using substances that interfere in the process of carcinogenesis.

Purpose

Clinical trials are currently investigating chemoprevention for people at high risk of certain cancers. For instance, to prevent breast cancer in the second breast of women who have already been treated for breast cancer, or women who have never had breast cancer but are determined to be at high risk; or to prevent colon cancer in people with a genetic predisposition for the cancer. Individuals not at a particularly high risk can use behavioral and dietary modifications for chemoprevention. Since the 1980s, the National Cancer Institute has identified more than 1,000 natural and synthetic chemicals with some degree of cancer preventive activity. Currently, more than 400 potential agents are under investigation for their ability to prevent cancer and at least 40 compounds or combinations are undergoing human clinical trials.

Chemopreventive agents have been identified that interact with all stages of carcinogenesis: initiation, promotion and progression. They work by inactivating carcinogens (cancer-causing agents), inducing enzymes, or as antioxidants. Later in the process they may inhibit tumor growth by acting as suppressors or stimulating apoptosis.

Description

Chemoprevention differs from chemotherapy in that it is used long before cancer develops to prevent cancer or to inhibit pre-cancer, possibly in at-risk individuals. Chemotherapy, on the other hand, seeks to kill cells that already have become cancerous. Chemoprevention uses natural products from foods or synthetic preparations. Because chemoprevention is used long term, it must be non-toxic, effective, easy to administer, and inexpensive. Few specific agents are currently advised for widespread clinical use since clinical trials that last up to 15 years are still ongoing.

Strategies for chemoprevention change often based on clinical trial results and scientific discoveries. For example, scientists completed the first map of the human genome (genetic makeup) in mid-2002. Since that time, cancer research has evolved rapidly. Epigenetic events, or the alterations in gene expressions without certain DNA involvement, may lead to cancer chemopreventive drug development aimed at tumor suppressor genes.

Dietary factors and lifestyle changes are important areas in chemoprevention. It is estimated that through dietary improvements there could be a 50% reduction in colon and rectal cancers, a 25% reduction in breast cancer and a 15% reductions each in prostate, endometrial and gallbladder cancers. Cancers of the stomach, esophagus, pancreas, ovaries, liver, lung, and bladder also may be affected by dietary factors. However, these improvements probably should come from the diet rather than from dietary supplements. In 2003, the U.S. Preventive Services Task Force released a report stating that evidence was insufficient to recommend for or against use of vitamin supplements to help prevent cancer. The task force recommended against supplementation with beta carotene because of higher incidence of lung cancer among those who used certain levels of beta carotene supplements.

Phytochemicals from food are a source of many chemopreventive agents. Garlic alone contains 30 cancer preventing compounds including selenium. Broccoli contains indole-3-carbinol as well as phenethylisothio-cyanate, a sulfur-containing compound. Soy products contain phytoestrogens such as genistein. Tea, both black and green, contains an abundance of polyphenols such as the catechins that have antioxidant and anti-cancer activity. Compounds in tea also have antiestrogen activity and can modulate detoxification enzymes. Cur-cumin from the spice turmeric is gaining attention as a chemopreventive agent. It is both an anti-inflammatory agent and an antioxidant. In laboratory animals curcumin has shown inhibition toward colon, breast, and stomach cancer.

Chemoprevention of Breast Cancer

Antiestrogens can counteract the growth effect estrogen has on some breast cancers. Two antiestrogens, tamoxifen and raloxifene, have been shown in clinical trials to prevent breast cancer in women at high risk for the disease. As a result of these trials, tamoxifen has been approved by the FDA as a preventive therapy as well as a treatment. Other antiestrogens, including soy isoflavones, are still under investigation. The synthetic retinoid, fenretinide, also shows promise in preventing breast cancer. Also under investigation are indole-3-carbinol from broccoli.

Chemoprevention of Colon Cancer

Because there are more identifiable tumor markers known for colon cancer, the evaluation of chemopreventive agents can be a shorter process. The recurrence of polyps rather than the development of malignant cancer can be used as an endpoint. Inflammation has been linked to cancer for some time and the anti-inflammatory agents sulindac and sulindac sulfone as well as specific cyclooxygenase-2 inhibitors are proving useful in preventing colon cancer. Adding fruits and vegetables to the diet also appears from epidemiological studies to have a protective effect on colon cancer.

Chemoprevention of Prostate Cancer

Antiandrogens and antiestrogens are both important in preventing prostate cancer. Finasteride is under investigation as an anti-estrogen to prevent prostate cancer in at-risk men. Finasteride is a drug that can reduce the levels of dihydrotestosterone, which is associated with prostate enlargement and possibly cancer. It has been used to treat enlarged prostate and is currently being investigated to prevent prostate cancer in men over the age of 55 years. Men at an increased risk for prostate cancer include those with a history of prostate cancer, those with a high-fat diet, increasing age, and those of African-American descent. Soy products and indole-3-carbinol may also be effective for this reason. Lycopene, a vitamin A-like compound found in tomatoes and other red fruits and vegetables is associated with a decreased risk of prostate cancer. Both selenium and tea may also have chemopreventive effects on prostate cancer.

Chemoprevention of Skin Cancer

The incidence of skin cancer has dramatically increased in recent years, probably due to the popularity of sun tanning. Compounds under investigation for the prevention of skin cancer include compounds from tea, silymarin from milk thistle, vitamin A and coumarins found in a number of plants.

Recommendations

Changes in lifestyle can significantly affect an individual's risk for cancer. It is estimated that 32% of colon cancers are related to physical inactivity, which may also play a part in other cancers. Tobacco accounts for 30% of all cancers, not just lung cancer. Alcohol consumption is related to cancers of the oral cavity, pharynx, larynx, esophagus, and liver, and possibly colorectal and breast cancers. The combination of alcohol and tobacco is especially dangerous. The main cause of skin cancers is exposure to UV radiation. Fair skinned individuals are at an increased risk. Obesity puts an individual at an increased risk of death from uterus, gallbladder, kidney, stomach, colon, breast, and prostate cancers.

The lifestyle recommendations from the American Cancer Society for preventing cancer include:

• Maintain a desirable body weight.
• Eat a variety of foods.
• Include both fruits and vegetables in the daily diet.
• Eat more high-fiber foods.
• Cut down on total fat intake.
• Limit consumption of alcoholic beverages.
• Limit consumption of salt-cured, smoked and nitrite preserved foods.

Risks

Because chemopreventive agents can be administered in high doses and for long periods of time, the risk of side effects is increased. During the 1980s, the CARET study found that beta-carotene actually increased the risk of lung cancer in male smokers. Studies of tamoxifen to prevent breast cancer show the drug can increase the risks of uterine cancer, and cause other serious side effects. Long-term use of non-steroidal anti-inflammatory drugs to prevent colon cancer can result in gastrointestinal problems and liver toxicity. Current recommendations are to increase consumption of fruits, vegetables and fiber in the diet rather than taking supplements.

Resources

Books

American Institute for Cancer Research. Stopping Cancer Before it Starts. New York: Golden Books, 1999.

Kelloff, Gary J, James A. Crowell, Vernon E. Steele, Ronald A. Lubet, et. al. "Progress in Cancer Chemoprevention." In Cancer Prevention: Novel Nutrient and Pharmaceutical Developments. Annals of The New York Academy of Sciences, vol. 889, edited by H. Leon Bradlow, Jack Fishman, and Michael P. Osborne. New York: The New York Academy of Sciences, 1999.

Periodicals

Koplevich, Levy, James A. Crowell, and Judith R. Fay. "The Epigenome as a Target for Cancer Chemoprevention." Journal of the National Cancer Institute December 3, 2003.

Rao, Chinthalapally V., Abraham Rivenson, Barbara Simi, and Bandaru S. Reddy. "Chemoprevention of Colon Cancer by Dietary Curcumin." 768 Annals New York Academy of Sciences 1995: 201–204.

"Routine Vitamin Supplementation to Prevent Cancer and Cardiovascular Disease: Receommendations and Rationale." American Family Physician 68 (December 15, 2003): 2422.

Other

Dresbach, Sereana Howard and Amy Rossi. "Chemoprevention—The Answer to Cancer?" Ohio State University Extension Fact Sheet, Family and Consumer Sciences. [cited 4 July 2001]. .

Greenwald, Peter and Sharon S. McDonald. "Cancer Prevention: The Roles of Diet and Chemoprevention." Cancer Control Journal. [cited 4 July 2001]. .

—Cindy L. A. Jones, Ph.D.; Teresa G. Odle

(kē'mō-prĭ-vĕn'shən, kĕm'ō-)
n.

The use of chemical agents, drugs, or food supplements to prevent disease.