Colon and Rectal Cancers

Description

Alternative Names

Prevention

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very common agents available over-the-counter and by prescription that are used to relieve pain. They have specific actions against prostaglandins and the enzymes called cyclooxygenases (COX 1, COX 2, or both), which have with colon cancer risk.

• Over-the-Counter NSAIDs. Over the counter NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin, Rufen), and naproxen (Aleve). A number of studies have reported that taking these agents at doses similar to those commonly taken to relieve arthritis pain is associated with a lower rate of colorectal cancer by up to 40% over the long term. For example, landmark studies in 2003 reported protection in high-risk patients with even low daily doses of aspirin (81 mg, one "baby" aspirin). Long-term use of any NSAID increases the risk for gastrointestinal bleeding and ulcers, however, and experts to not yet recommend NSAIDs for prevention of colon cancer. They are certainly no substitute for regular screening procedures to catch cancer at an early, and curable, stage.
• Prescription NSAIDs for Prevention of Hereditary Cancers. Some studies report that the potent prescription NSAIDs indomethacin and sulindac can cause regression of polyps and stave off colon cancer for several years in people with FAP. A 2002 study in children and young adults with FAP who were given sulindac for four years, however, did not show any reduction in new polyp formation. More research is needed to determine if NSAIDs have preventive value in high-risk individuals.
• COX-2 Inhibitors. Selective COX-2 inhibitors, such as celecoxib (Celebrex) and rofecoxib (Vioxx), are newer enzymes that only block the enzyme cyclooxygenase-2 (COX-2), which has been specifically linked to colon cancer. Both are being investigated for possible protection against colon cancer. Early studies indicate that celecoxib may help prevent new growth and retard the growth of existing polyps. Experts hope, then, COX-2 inhibitors may prevent colon cancer without posing as high a danger of bleeding and ulcers as standard NSAIDs. Celecoxib has now been approved for patients with familial adenomatous polyposis (FAP). Studies report significant reduction in disease activity in the large and small intestines of these patients.

In some studies, combining NSAIDs with the cholesterol-lowering drugs known as statins (for example, lovastatin, pravastatin, simvastatin) significantly lowered the rate of colon cancer compared to taking NSAIDs alone. Experts are hoping that such combinations may allow lower NSAIDs dosages, thereby reducing the risk for side effects, but further study is required. Preliminary evidence presented at the 2004 American Society for Clinical Oncology (ASCO) conference indicated that statins themselves may help reduce the risk of colorectal cancer, but more research is needed.

Complications. It is important to note that NSAIDs, even in low doses, can cause gastrointestinal bleeding and ulcers in some people. In fact, studies estimate NSAID-related deaths in the United States at 10,000 to 20,000 per year, and NSAID-related hospitalizations at 100,000 per year. COX-2 inhibitors may have fewer of these side effects, although long-term studies are still needed.

Exercise

Studies have indicated that regular, even moderate exercise (30-minute daily jog or 60-minute daily walk) reduces the risk of colon cancer. Regular activity may be the most important lifestyle component in decreasing colon cancer risk. In one 2002 study, women who performed strength training exercises twice a week reduced several markers for both breast and colon cancer. The ultimate impact of these changes on breast and colon caner remains to be determined.

Estrogen in Women

Estrogen has been associated with a lower risk for colon cancer, perhaps because of specific enzymes the prevent cell proliferation. Agents containing estrogen, then, may help high-risk women:

• There is some evidence that hormone replacement therapy (HRT) reduces the risk of colon cancer in postmenopausal women. It carries other risks, however, including a higher risk for breast and uterine cancer and blood clots. A 2004 study published in the New England Journal of Medicine found that while short-term use of estrogen plus progestin reduced the risk of developing colon cancer, combination HRT users who were diagnosed with the disease had more advanced forms of the cancer. Older women who are at higher risk for colon cancer might discuss risks and benefits of HRT with their physician.
• Oral contraceptives may reduce younger womens risk of colon cancer. Duration of use does not seem to be associated with decreased risk, but protection appears stronger for women who have used oral contraceptives more recently.

Ursodiol

Ursodiol is a drug sometimes used to treat gallstones or a rare inflammation of the bile ducts associated with ulcerative colitis. It helps reduce deoxycholic acid levels, a bile acid that has tumor-promoting properties. Animal studies have indicated colon cancer protection with the drug, but a 2002 study found no protective benefits for humans.

Melatonin

Melatonin is a hormone found in the brain that is mostly associated with its role in sleep. Researchers have also observed that the gastrointestinal tract is rich in melatonin, and that the hormone may have properties that help prevent ulcers, reduce acid secretion, and improve blood flow. It is not known whether this would help prevent colon cancer, but it appears to warrant some research. It should be stressed that melatonin is currently classified as a dietary supplement and not as a drug, so its purity, safety, and effectiveness are uncontrolled in the US. Melatonin is a powerful hormone that can have major effects, many still unknown, on many parts of the body. The bottom line is that at this time, people who take melatonin are experimenting on themselves.