Colon Cancer Prevention

Introduction to colon cancer prevention

Cancer of the colon and the rectum (also known as colon cancer or colo-rectal cancer) is a malignant growth arising from the inner lining of the colon or rectum. Colo-rectal cancer is a major cause of cancer-related deaths among men and women in the United States.

The good news is that colo-rectal cancer is both curable and preventable if it is detected early and completely removed before the cancerous cells metastasize (spread) to other parts of the body. Colo-rectal cancer can be prevented by removing colo-rectal polyps before they grow and change into cancers, or by using natural substances or man-made chemicals to prevent the colo-rectal polyps from changing into cancer. (Using natural substances or chemicals to prevent cancer is called chemo-prevention).

Measures to prevent diseases usually fall into one of five categories of safety and effectiveness. These categories are:

1. Measures that have scientifically-proven effectiveness and long-term safety
2. Measures that probably are effective but may have long-term, adverse side effects
3. Measures that probably are effective, and safe
4. Measures that have been found to be ineffective
5. Measures that have no scientific basis and no studies to measure effectiveness and safety

What measures to prevent colo-rectal cancer have proven effectiveness and long term safety?

Colonoscopy and flexible sigmoidoscopy (along with digital rectal examination and stool occult blood testing) are the primary and most important tools for both preventing colo-rectal cancers and detecting early colo-rectal cancers.

Most colo-rectal cancers arise from colo-rectal polyps (small growths on the inner lining of the colon and the rectum). Even though colo-rectal polyps are initially benign, they can grow and change into colo-rectal cancers over a period of time ranging from five to twenty years. A large study that was conducted in several research centers in the United States showed that patients who had their polyps removed (usually via colonoscopy) had a 90% decrease in colo-rectal cancer.

What measures to prevent colo-rectal cancer probably are effective but may have long term adverse side effects?

NSAIDs (non-steroidal anti-inflammatory drugs) are widely used in the treatment ofarthritis and other inflammatory conditions of the body. Some examples of NSAIDs include aspirin, sulindac, ibuprofen,naproxen, and piroxicam. How NSAIDs prevent colon cancer and polyps is under investigation. (NSAIDs are potent inhibitors of prostaglandins in the body, and prostaglandins may be important in the formation of polyps.)

In a 6-year study of approximately 700,000 men and women reported in The New England Journal of Medicine in 1991 (volume 325, pages 1593-6), the death rates from colo-rectal cancer were compared between groups with different levels of aspirin consumption. It was found that adults who consumed aspirin regularly (more than 16 times per month) had a 40% lower death-rate from colo-rectal cancer than adults who did not consume aspirin regularly.

The most impressive chemoprevention data relate to sulindac. Ten patients with familial polyposis coli, a genetic disease that causes individuals to form many colo-rectal cancers, were studied. These patients had already had their colons removed to prevent colon cancer, but the distal part of the colon, the rectum, was not removed, and there still were pre-cancerous polyps in the rectum. Sulindac was found to cause regression (and sometimes disappearance) of the rectal polyps after 4 months of treatment. The study was reported in the journal, Gastroenterology, in 1991 (volume 101, pages 635-639). Unfortunately, polyps returned within a few months if sulindac was stopped or the patient was switched to a placebo.

Why aren't doctors recommending NSAIDs for colorectal cancer prevention? Because NSAIDs can cause stomach ulcers, intestinal bleeding and, sometimes, adverse effects on the liver and kidneys. Even though safer NSAIDs have been developed, doctors generally are reluctant to recommend aspirin or other NSAIDs for preventing colo-rectal cancer until data on their effectiveness and long-term safety are available.

When prescribing an agent for prolonged periods of time to prevent a disease that may or may not occur, the last thing a doctor would want is for that agent to cause adverse site effects in a healthy person.

What measures to prevent colo-rectal cancer probably are effective and safe?

Oral supplements of calcium and folic acid, diets high in fruits and vegetables and low in saturated fat and red meat, avoidingobesity, regular exercise, and quitting cigarette smoking are safe measures that probably prevent colo-rectal cancer.

Calcium supplements have been shown in animal and human studies to decrease the number of pre-cancerous polyps. Fruits and vegetables contain many chemicals that inactivate cancer-causing chemicals (carcinogens). Obesity, a sedentary life style, cigarette smoking, and high red meat consumption have been linked to an increased risk of colo-rectal cancer. In a large study of nurses, those who took multivitamins that contained folic acid for decades had less colo-rectal cancer than women who did not take multivitamins.

These measures are considered only "probably" effective because long-term, large-scale, properly designed clinical trialshave yet to be performed to establish conclusively that these measures actually prevent colo-rectal cancer.

Doctors are willing to prescribe an agent without conclusive proof of its effectiveness as long as it is safe. In many instances, conclusive proof may be many years away.

What prevention measures have been found to be ineffective?

Anti-oxidants are believed to have anti-cancer effects, but clinical trials using the anti-oxidant vitamins C and A have shown no benefit in preventing colo-rectal cancer.

Many agents or measures that are promising because they have theoretical benefits fall short of expectations when subjected to rigorous clinical trials.

What about genetic testing for colon cancer?

Genetic testing using blood tests are now available to identify patients with hereditary colon cancer syndromes. Hereditary colon cancer syndromes are caused by specific inherited mutations that are sufficient in themselves to cause colon polyps, colon cancers, and non-colonic cancers. Hereditary colon cancer syndrome can affect multiple members of a family. Approximately 5% of all colon cancers in the US are due to hereditary colon cancer syndromes. Patients who have inherited one of these syndromes have an extremely high risk for developing colon cancer, approaching 90%-100%. Fortunately, blood tests are now available to test for these hereditary colon cancer syndromes, once a syndrome has been suspected within a family.

Familial adenomatous polyposis (FAP).Familial adenomatous polyposis, or FAP is a hereditary colon cancer syndrome in which the affected family members develop large numbers (hundreds, sometimes thousands) of colon polyps starting in their teens. Unless the condition is detected and treated early (treatment involves removal of the colon), a family member with the FAP syndrome is almost sure to develop colon cancer. Cancers most commonly begin to appear when patients are in their 40's, but can appear earlier. These patients also are at risk of developing other cancers such as cancers of the thyroid gland, stomach, and the ampulla (the part of the duodenum into which the bile ducts drain).

Attenuated familial adenomatous polyposis (AFAP). Attenuated familial adenomatous polyposis, or AFAP is a milder version of FAP. Affected patients develop less than 100 colon polyps. Nevertheless, they are at high risk of developing colon cancers at a young age. They are also at risk for stomach and duodenal polyps.

Hereditary nonpolyposis colon cancer (HNPCC). Hereditary nonpolyposis colon cancer, or HNPCC, is a hereditary cancer syndrome in which affected family members tend to develop colon cancers, usually in the right colon, in their 30's to 40's. Certain HNPCC patients also are at elevated risk for developing uterine cancer, stomach cancer, ovarian cancer, cancers of the ureters (the tubes that connect the kidneys to the bladder), cancers of the bile ducts (the ducts that drain bile from the liver to the intestines), and cancer of the brain and skin.

MYH polyposis syndrom. The MYH polyposis syndrome is a recently discovered hereditary colon cancer syndrome. Affected patients typically develop 10-100 polyps during their 40's and are at high risk for developing colon cancer. The MYH syndrome is inherited in an autosomal recessivemanner with each parent contributing one copy of the mutant gene. Most people with the MYH syndrome do not have a multigenerational family history of polyps or cancer of the colon but may have brothers or sisters with it.

Who should consider genetic counseling and testing?

Genetic counseling followed by genetic testing should be considered for individuals as well as their family members when there are:

• Individuals in the family with early onset of colon cancer, before age 50
• Individuals in the family with numerous colon polyps
• Families in which multiple members have colon cancer
• Families with members with numerous colon polyps
• Families with members having colon cancers at young ages
• Families with members having certain non-colon cancers such as cancers of the uterus, thyroid, ureters, ovaries, small intestine, etc.

Genetic testing without prior counseling is discouraged because of the extensive family education that is involved and the complicated nature of interpreting the test results.

Why is genetic counseling and testing important in hereditary colon cancer syndromes?

Patients who have hereditary colon cancer syndromes usually have no symptoms and are unaware that they have colon polyps or early colon cancers. They usually will develop colon cancers early in life (often before ages 40-50). Therefore, to prevent colon cancers in patients with hereditary colon cancer syndromes, colon screening must begin early. For example, patients with FAP should have annual flexible sigmoidoscopies starting at age 12, patients with AFAP should have annual colonoscopies starting at age 25, and patients with HNPCC should have colonoscopies beginning at age 25 (or 10 years younger than the earliest colon cancer diagnosed in the family, whichever is earlier). The current screening recommendations for the general population (fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy beginning at ages 40-50) are inadequate for most patients with hereditary colon cancer syndromes.

Genetic counseling and testing are important to identify patients and family members with hereditary colon cancer syndromes so that screening with flexible sigmoidoscopies and colonoscopies can begin early and, if necessary, the colon can be removed surgically to prevent colon cancer. Moreover, depending on which hereditary colon cancer syndrome is present, early screening for other types of cancer such as ovarian, uterine, stomach, ureter, and thyroid may be appropriate.

What can be done now to prevent colorectal cancer?

1. Eat a diet high in fruits and vegetables and low in fat and red meat. (This diet also is good for cardio-vascular health.)
2. Take oral calcium supplements and one multivitamin a day that contains 400 micrograms of folic acid. (Calcium supplements also are necessary for maintaining the strength of bones, and folic acid may be good for cardio-vascular health.)
3. Lose excess weight, exercise regularly, and stop smoking cigarettes. (This also is good for cardio-vascular health.)
4. Undergo screening tests for colo-rectal polyps and cancer. (Please visit Colon Cancer: Screening and Surveillance.)
5. If one has family members with numerous colon polyps, early onset of colon cancers or other cancers such as uterine, stomach, thyroid, and ovarian cancer, talk to your doctor about genetic counseling and testing.