COLORECTAL CANCER 101

Although it may not rank at the top of most of our lists of health concerns, colon cancer is the third leading cause of cancer deaths in women, exceeded only by cancers of the lung and breast. This year, about 66,000 women will be diagnosed with the disease, and more than 27,000 are expected to die of it.

Yet the death rate from colon cancer has been steadily declining since the 1940s, when it claimed 27 women in 100,000 -- a figure equal to that for breast cancer at the time. In 1992, the last year for which statistics are available, the rate had dropped to 15 in 100,000.

The story in these numbers is that colon cancer, when detected in the early stages, is a highly treatable and often curable disease. Moreover, as observational studies indicate, it may also be preventable.

The genesis of colon cancer
Colon cancer often arises in adenomatous polyps, benign tumors that are most often found in people over age 50. These polyps may protrude from the bowel wall like small mushrooms (tubular polyps) or appear as flat, spreading growths along its surface (villous adenomas). Villous adenomas are more likely than tubular polyps to transform to cancer. The likelihood that an adenomatous polyp contains a cancer becomes substantial when the polyp is wider than one inch.

Only a small percentage of polyps or adenomas become cancerous, and those that do aren't transformed overnight. By comparing the DNA of cells taken from typical colon epithelium to that from benign polyps and malignant colon tumors, scientists have determined that it takes a series of genetic changes for tumors to form and to progress to malignancy.

These alterations appear to occur in one of three types of genes -- DNA-repair genes, which prevent mutations from occurring; tumor suppressor genes, which keep cells dividing normally; and oncogenes, which stimulate tumor growth. If, over the years, these genes are damaged, lost, turned off, or, in the case of oncogenes, activated inappropriately, the cells will proliferate recklessly. As genetic damage accumulates, tumors become more resistant to treatment.

Symptoms
Colon cancer usually develops silently. When symptoms do occur, they vary according to the location and the severity of the tumor. The following are among the most common:

Bleeding. Colon cancers -- as well as benign polyps -- can ooze blood steadily or intermittently, often producing black or bloody bowel movements.
Anemia may result from continued blood loss.
Constipation. Gradually worsening constipation without apparent cause is reason for concern.
Pain in the lower abdomen can be due to an obstruction caused by the tumor.
Weight loss and loss of appetite that seem to occur for no reason are signs of advanced cancer.
Screening
The declining death rate is primarily due to aggressive screening measures aimed at identifying colon cancer, or even a precancerous condition, in the early stages. The following schedule is recommended by the American Cancer Society:

Digital rectal exam. This procedure, in which the doctor inserts a lubricated gloved finger in the rectum to feel for abnormalities, should be part of the annual physical for everyone over 40.
Fecal occult blood test. This test detects blood -- usually from the higher regions of the colon -- that has become incorporated in stools. It entails applying hydrogen peroxide to stool samples smeared on cards. (Blood in the stool will produce a blue color when the peroxide is added.) Although kits are available at drug stores, most cards are issued by and returned to the doctor Occasionally, the physician might use stool acquired during a rectal exam. The most accurate results are acquired after abstaining from meat and certain other foods for a few days. A test is recommended annually for people over 50.
Sigmoidoscopy. This is a procedure in which the doctor examines the rectum and lower colon through a lighted flexible tube. Although it is recommended every 3-5 years for people over age 50, health insurance may not cover this test for people without symptoms.
Diagnosis
The following diagnostic tests may be used when symptoms suggest colon cancer The procedure employed depends on the type of symptom.

Flexible sigmoidoscopy is often the first approach when the symptom is bright red blood, which could be emanating from several sources, including hemorrhoids, proctitis, benign polyps or malignant tumors.
Colonoscopy, an exam with a longer lighted tube, affords a view of the entire colon. It is used when an occult blood test is positive or to check for additional polyps if the doctor discovers an adenomatous polyp with the sigmoidoscope. Regular colonoscopies are recommended for individuals at high risk for colon cancer (see box.) The polyps that are seen are removed and examined for cancer cells.
Barium enema. An x-ray taken after the administration of a barium enema produces an image of the colon. If polyps are found, colonoscopy is necessary.
Treatment
When malignancy is established, colon cancer is classified by stages, depending on the spread of the primary tumor and the degree of metastasis -- the presence of cancer cells in nearby lymph nodes or in other regions of the body. Surgery, sometimes followed by radiation or chemotherapy, is the standard approach to colon cancer. However, as with other types of cancer,the treatment varies with the stage of the disease as explained in the chart at right. Colostomy-- in which the surgeon creates an opening called a stoma in the abdomen and sutures the remaining colon to it -- is rarely necessary.

Prevention
Because colon cancer is far more common in the industrialized nations than in less developed regions of the world, bring habits seem at least partially responsible. The following appear to reduce risk.

Diet. Low-fat, high-fiber regimens with several daily servings of fruits, vegetables, and cereals are associated with reduced risk. A diet rich in calcium and folate -- a micronutrient in leafy green and yellow vegetables -- may reduce risk.
Nonsteroidal anti-inflammatory drugs. Although no one seems to be certain why these over-the-counter drugs work, people who take them for several years appear to have lower rates of colon cancer.
Smoking cessation. As with lung and cervical cancers, cigarette smoking increases risk.
Postmenopausal estrogen. More than half of the epidemiologic studies reported to date have indicated a 30-40% reduction in the risk of colon cancer among women who have used estrogen after menopause. An observational study of more than 400,000 women has indicated that those who have used estrogen have a 29% lower risk of fatal colon cancer than do nonusers. There is some speculation that estrogen reduces concentrations of bile acids, which may promote tumor growth in the colon. However, these observations need to be tested in randomized, controlled studies.
Polyp removal. Removing polyps and adenomas eliminates a potential site of malignancy.
RISK FACTORS
Family History -- Having colon cancer in the family increases risk somewhat, but familial adenomatous polyposis (FAP). which confers an almost certain chance of developing colorectal cancer by one's 40s, or hereditary nonpolyposis colon cancer (HNPCC) indicates high risk. Genetic tests are available for both FAP and HNPCC, and people found to have the mutations that are responsible should have frequent colonoscopies beginning in adolescence.

Adenomatous Polyps
Inflammatory Bowel Disease -- Severe ulcerative colitis, Crohn's disease

Age -- Although age isn't as important a factor as those listed above, the risk of colon cancer increases after age 50.

STAGES OF COLON CANCER
Treatment 5-Year Survival

Stage I:

Tumor confined Bowel resection 94.3%
to colon wall

Stage II

Tumor through Bowel resection; 84.4%
colon wall occasionally
radiation

Stage III

Colon tumor and Bowel resection; 56.6%
malignant lymph nodes radiation;
chemotherapy with
5-fluorouracil
(5-FU) and
levamisole.;
experimental immune
system boosters

Stage IV

Colon tumor and Bowel resection; 2.4%
metastases to other radiation,
regions of the body occasionally surgery
to remove liver
Metastases; 5-FU;
other drugs and
immune boosters used
experimentally

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