2006-Sep-15
by JACK DANIELS

Hereditary colorectal cancer is cancer of the colon or rectum that develops chiefly as the result of inherited factors.

Description of colorectal cancer The colon, or the large intestine, is a long muscular tube that absorbs water from stool and advances the stool towards the rectum. The rectum works in conjunction with the anus to coordinate the process of defecation. The colon and rectum are jointly referred to as the colorectum.

A neoplasm is a portion of abnormal tissue that grows rapidly and out of control. Cancer is the malignant type of neoplasm. Colorectal cancer is a relatively common and dangerous cancer. Tumors originate in the mucosa, or inner lining of the colorectum, and grow inwardly. Eventually, the tumor spreads outwardly until it reaches lymph nodes or other organs in the abdomen. Ultimately, cancer cells may detach from the original tumor and spread to distant parts of the body (such as the liver, lungs, bone, and brain) in a process called metastasis.

The development of colorectal cancer is not a random event, but rather arises in a sequential fashion. The first easily detected step is the appearance of adenomatous polyps. Polyps are grossly defined as elevations of a surface. An adenomatous polyp is derived from the glandular elements of the mucosa. A person may have any number of colorectal adenomatous polyps. Eventually, one or more of these polyps may transform into a cancer. The risk of colorectal cancer increases with the number of polyps. Larger polyps are also more likely to become cancerous than smaller ones. The factors that initiate this adenoma-cancer sequence are inherited and/or acquired from the environment.

Colorectal cancer occurs in certain families much more often than expected by chance alone. In fact, an important and common risk factor for the development of colorectal cancer is the occurrence of colorectal cancer in the family. About 10% of people have a first-degree relative with colorectal cancer. Having a first-degree relative with colorectal cancer increases the chance of developing colorectal cancer by two- to three-fold. The risk becomes even higher when colorectal cancer occurs in a relative at an early age (before 50 years of age) or when more than one relative has the cancer. This suggests that susceptibility of developing colorectal cancer in affected families is due to inherited factors, although shared exposure to environmental stimuli may play a role. Scientists are investigating the genetic factors that may be responsible for the increased risk of colorectal cancer in these cases of common inheritance.

The vast majority of cases of colorectal cancer are sporadic; that is, they occur in the absence of a hereditary syndrome, although familial risk may be involved. But rarely, colorectal cancer is inherited as part of a well-defined syndrome. These syndromes altogether account for about 2-5% of all cases of colorectal cancer.

• Familial adenomatous polyposis

In the syndrome of familial adenomatous polyposis (FAP), adenomas develop in the colon and rectum early in life, at an average age of 15 years. Eventually, hundreds to thousands of adenomas will develop. The presence of such a large number of adenomas ensures that at least one of these adenomas will develop into cancer if the colon is not surgically removed. In people with FAP, the average age of occurrence of colorectal cancer is 39. Some patients will develop cancer in their teens and almost every patient will have cancer by age 45.

Other types of polyps are also common in patients with FAP. Polyps may develop in the stomach or duodenum. Those in the stomach are benign, while those in the duodenum may become malignant. The cancer risk in these other polyps is much less than the risk associated with the colorectal polyps. Patients with FAP may also have abnormalities outside the gastrointestinal tract, such as osteomas, desmoid tumors, extra teeth, and hypertrophy of the retinal pigment epithelium.

Three variants of FAP have been identified. Gardner syndrome is a rare variant of FAP characterized by colorectal polyps and a marked prominence of extraintestinal growths. Examples of the growths include osteomas, epidermoid cysts, and desmoid tumors. Although these growths usually present only cosmetic problems, desmoid tumors can occasionally compress nearby tissue in a harmful way.

Turcot syndrome is another rare type of FAP. Patients with this syndrome have the typical colorectal polyps, as well as malignant tumors of the central nervous system such as medulloblastoma, astrocytoma, ependymoma, and glioblastoma multiforme.

Patients with the attenuated adenomatous polyposis coli form of FAP have many colonic polyps, but not the hundreds or thousands seen in typical FAP. The chance of developing colon cancer approaches but does not reach 100%, and colon cancer usually appears later than in patients with typical FAP.

• Hereditary nonpolyposis colorectal cancer

Patients with hereditary nonpolyposis colorectal cancer (HNPCC) have about an 80% risk of developing colorectal cancer if untreated. They may have more polyps than the general population, but not the hundreds or thousands of polyps associated with FAP. The average age for the development of cancer is 45 years old. Frequently, a patient with HNPCC will have multiple cancers at the same time (synchronous) or may develop cancers at different time periods (metachronous).

Extraintestinal cancers sometimes occur in HNPCC. The most common is uterine cancer, but other examples include cancer of the uterus, stomach, small intestine, pancreas, kidney, and ovary.

The Amsterdam criteria are clinical criteria for the diagnosis of HNPCC in a family:

• At least three relatives with colorectal cancer, one of whom must be a first-degree relative of the other two.
• Colorectal cancer involving at least two generations.
• One or more cases of colorectal cancer before the age of 50.

Muir-Torre syndrome is a rare form of HNPCC. In addition to polyps and cancer of the colon and rectum, patients exhibit various types of skin cancer.

Treatment of Colorectal cancer The treatment of sporadic colorectal cancer requires surgical removal of the tumor and surrounding tissue. Chemotherapy or radiation therapy may also be necessary. But the treatment of colorectal cancer in the hereditary syndromes is more aggressive. In these cases, the entire colon must be removed, since cancer will almost certainly develop in any remaining colon. Sometimes the rectum is also removed; alternatively, the patient may undergo frequent examination of the rectum for polyps or cancers. Experts strongly recommend that individuals with known FAP should consider surgical removal of the colon and/or rectum early in life as a prophylactic measure, before cancer is diagnosed. Although the role of prophylactic surgery in patients with HNPCC is less well-defined, many experts favor it. The patient faces a choice between prophylactic surgery and frequent, lifelong screening.

Some studies have shown that the drug sulindac may reduce the number of adenomatous polyps that develop in FAP and its variants. In addition, certain nonsteroidal anti-flammatory drugs such as aspirin may also reduce the incidence of colorectal cancer in general.

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