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When a postmenopausal woman or adult man develops such symptoms in the absence of an obvious cause, CRC should be suspected. Pain in the lower abdomen is an occasional symptom of tumors located in the transverse or left colon. These patients are more likely to notice a change in bowel habits, as either diarrhea or constipation can occur owing to a constricting lumen. The stool may be dark or maroon-colored, and passage may be associated with bloody mucus. Weight loss and fever are occasionally reported as well but seldom as the sole presenting symptom. The first signs of colon cancer may be produced by metastatic disease. Colon cancer metastasizes to the liver and lung, whereas rectal cancer metastasizes primarily to the lung and bone. An otherwise asymptomatic patient may have pruritus and jaundice due to liver involvement. Ascites, enlarged ovaries, and scattered deposits in the lungs may also result from the otherwise undetected presence of CRC.

Obstruction and perforation are the conditions most often associated with the acute presentation of CRC. Obstruction of the large bowel is highly suggestive of cancer, particularly in older patients. Complete obstruction occurs in up to half of patients, depending on the location of the tumor. Long-term survival rates are poorer for patients who have obstruction at the time of diagnosis. Perforation is a surgical emergency and may precipitate complications such as peritonitis and abscess formation.

Risk Factors

Polyps
Polyps are a risk factor for CRC, particularly if they are adenomatous in type. Siblings and parents of patients with adenomatous colorectal polyps have a 1.78 relative risk for developing CRC. The age at the time of polyp diagnosis is an important prognostic factor for the risk of cancer development. Siblings of patients with adenomatous polyps diagnosed before age 60 have a 2.59 relative risk for developing CRC. Polyp size and histology are directly related to the risk of CRC, with villous polyps larger than 2 cm having a 50% greater chance of containing cancer than smaller or nonvillous polyps.

There is concern that a small distal colorectal polyp, whether adenomatous or hyperplastic, is a proximal neoplasm marker. In study of 366 patients without a history of CRC or polyps, Pennazio et al demonstrated that 34% of patients with distal small colorectal polyps also had proximal polyps noted on colonoscopic examination. These proximal lesions might have been missed had colonoscopy not been performed.

Familial Adenomatous Polyposis
Familial adenomatous polyposis is an autosomal-dominant disease, with an occurrence rate of 1:7000 to 1:10,000 individuals. The colon is virtually completely lined with polyps. Approximately 50% to 75% of these patients develop CRC by age 35 if colectomy is not performed. Diagnosis is by genetic testing of family members.

Dietary Factors
Dietary fat increases bowel transit time and increases the concentration of fecal bile acids, such as cholic and deoxycholic acid. These bile acids act as potential carcinogens on the colonic mucosa. In contrast to fat, fiber decreases bowel transit time and therefore exposure of the bowel to these carcinogens. Fiber, particularly wheat fiber, has been reported to have a protective effect against the development of CRC. A randomized study of high-dose wheat bran fiber and calcium supplementation reported reduced colonic levels of total and secondary fecal bile acids compared to controls. It is postulated that because bile acids may be carcinogenic, reduction of their concentrations in the colon may be the mechanism by which a high-fiber diet reduces the risk of developing CRC. However, a recent long-term study of 61,463 Swedish women (average 9.6 years of follow-up) revealed no decrease in the risk of colorectal cancer with high consumption of cereal fiber. The study did find that those women who had very low intake of fruits and vegetables had a much higher risk of developing colorectal cancer.

A diet rich in carbohydrates, fruits, and fiber may bestow a strong protective effect from adenoma development, whereas ingestion of a high-fat diet increase the risk of CRC development more than twice that of control groups. Dietary factors also play a role in the development of CRC in individuals who consume alcohol. Men who eat a diet low in folate and methionine accompanied by substantial consumption of alcohol (more than two drinks per day) have a 3.3 relative risk for development of colon cancer compared to individuals who drink less than two drinks a day and who have a balanced diet.

Environmental Factors
Environmental influences exert a definite influence on the development of CRC. Industrialized countries are at a relatively increased risk compared to less developed countries or countries that traditionally had high-fiber/low-fat diets. This point is exemplified by the fact that persons from a low-risk country who migrate to the United States over time develop CRC rates similar to those among native U.S. citizens. This increased rate of CRC is probably directly related to dietary changes that accompany migration (i.e., changing from a high-fiber/low-fat diet to a low fiber/high fat diet).

Only one-third of patients survive 5 years if nodal metastasis is present. Involvement of the deeper, pelvic nodes results in a 20% 5-year survival rate. Approximately 80% of recurrences occur in the first 2 years after treatment. The majority of recurrences occur near the site of the primary lesion. Seventy-five percent of patients with locally recurrent disease (limited to the vulva) can be salvaged with radical wide local excision. In contrast, patients who develop a groin recurrence are rarely curable, and palliative surgical resection is associated with a high risk of complications.

Smoking and Alcohol
Cigarette smoking and alcohol consumption have been reported to increase the relative risk of an individual to develop colonic adenomas and CRC. The relative risk of developing small adenomas is 3.6 for smokers with more than a 20-pack-a-year history. Alcohol consumption (especially when beer is the alcohol being consumed) increases the risk of developing CRC two- to threefold over baseline. Alcohol consumption and tobacco use are independently related to the risk of developing large colorectal adenomas.

Family History of Cancer
Although frequently neglected, a family medical history is an integral component of CRC risk detection. Cancer family syndrome, an autosomal-dominant disorder, incurs a 33% risk that a patient will develop cancer by the age of 50. Common cancers in these individuals include multiple adenocarcinomas of the colon (especially the proximal colon) or endometrium. Patients who have other types of cancer are at a relative increased risk of developing CRC. If a patient has a first-degree relative with CRC, the patient is at a two- to fourfold increased risk of developing CRC him- or herself.

Inflammatory Bowel Disease
There is a substantial increased risk of CRC in patients with ulcerative colitis, with the risk being inversely proportional to the age of onset of the colitis and directly proportional to the extent of colonic involvement. Twenty-five percent of patients with ulcerative colitis develop CRC after 25 years of disease. Crohn's disease is also associated with the development of CRC but to lesser degree than ulcerative colitis. Patients with Crohn's disease may have a 4- to 20-fold increased risk of developing CRC compared to the general population, but this association is less clear-cut than for ulcerative colitis.

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