Chemoprevention

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Chemoprevention

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 that 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, over 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 have already 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.

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, 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 may also be affected by dietary factors. Agents of importance in chemo-prevention include vitamins A, C and E as well as non-nutrient compounds from plants called phytochemicals.

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 phenethylisothiocyanate, 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 anti-estrogen activity and can modulate detoxification enzymes. Curcumin 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 towards colon, breast, and stomach cancer .

Chemoprevention of breast cancer

Anti-estrogens 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 preventative as well as a treatment. Other anti-estrogens including soy isoflavones are still under investigation. The synthetic retinoid, fenretinide, also shows promise in preventing breast cancer. Decreasing the amount of fat in the diet is also under investigation to prevent 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. A combination of beta-carotene, vitamin C and vitamin E are also under investigation as well as high-fiber wheat cereal supplements. Adding fruits and vegetables to the diet also appears from epidemiological studies to have a protective effect on colon cancer.

Chemoprevention of prostate cancer

Anti-androgens and anti-estrogens 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 and 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, colon, and prostrate cancers. Obese women are at a 55% greater risk of mortality from cancer than women of normal weight, while obese men are at a 33% greater risk of mortality from cancer.

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 1980's the CARET study found that beta-carotene actually increased the risk of lung cancer in male smokers. Studies of tamoxifen to prevent breast cancer can increase the risks of uterine cancer, cataracts and blood-clot formation. 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

Bal, Dileep G. Daniel W. Nixon, Susan B. Foerster, and Ross C. Brownson, "Cancer Prevention" In Clinical Oncology, edited by Murphy, Gerald P., Walter Lawrence, and Raymond E. Atlanta, GA: The American Cancer Society, 1995.

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, edited by Bradlow, H. Leon, Jack Fishman, and Michael P. Osborne. New York: The New York Academy of Sciences, 1999, vol 889.

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

PERIODICALS

Greenwald, Peter, "Chemoprevention of Cancer" Scientific American (September 1996).

Osborne, Michael, Peter Boyle, Peter and Martin Lipkin, "Cancer Prevention" Lancet 1997;349:SII27-30.

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

OTHER

Dresbach, Sereana Howard and Amy Rossi. "Chemoprevention—The Answer to Cancer?" Ohio State University Extension Fact Sheet, Family and Consumer Sciences <http://www.ag.ohio-state.edu/~ohioline/hyg-fact/5000/5051.html.> 4 July 2001.

Greenwald, Peter and Sharon S. McDonald. "Cancer Prevention: The Roles of Diet and Chemoprevention." Cancer Control Journal <http://www.moffitt.usf.edu/providers/ccj/v4n2/article2.html> 4 July 2001.

Cindy L. A. Jones, Ph.D.