There are several syndromes of an inheritable or familial nature which are characterized by polyposis and increased risk of colon cancer. Familial adenomatous polyposis (FAP) is the most important of these syndromes, yet it accounts for less than one percent of colon cancers in the United States. Affected individuals develop hundreds or thousands of polyps by their teen years, any one of which may develop into a cancer. Eighty percent of individuals with FAP will also develop small bowel adenomas and fifty percent will develop polyps in the stomach. Two thirds of individuals with FAP will also develop a condition in the eye retina known as congenital hypertrophy of the retinal pigment epithelium (CHRPE). CHRPE does not affect vision nor does it have a malignant character, but it is an important marker of the FAP syndrome and can be detected at birth by ophthalmologic examination.6

Preventive action, usually consisting of repeated examination or removal of the colon, is necessary, along with careful screening of family members for this disorder. The APC (adenomatous polyposis coli) gene, located on human chromosome 5, is believed to be the responsible gene for FAP. This gene is referred to as a tumor suppressor gene because decreased expression (availability) of the gene allows increased growth of abnormal cells.

Gardner syndrome is about half as frequent as FAP. It may affect both the small intestine as well as the colon. Other benign tumors affecting bone (osteomas), connective tissue (fibromas), fatty tissues (lipomas), the tissues lining the abdomen (desmoid tumors) and benign cysts of the sweat glands (sebaceous cysts) may be found. Some authorities consider Gardner syndrome to be a subset of FAP.

Oldfield and Turcot syndromes are related to Gardner syndrome. The former is associated with sebaceous cysts and the latter is associated with tumors of the central nervous system. These syndromes are quite rare.

Hereditary Non-Polyposis Colorectal Cancer (HNPCC). The name is somewhat misleading, because these forms of colon cancer do in fact arise from polyps, but individuals do not have an abundant proliferation of polyps as in the above mentioned polyposis syndromes. The polyps that are found in family members have an extraordinarily high likelihood of progressing to cancer. Therefore, it is felt that these individuals have a cancer gene, more than a polyp gene.

The syndrome of family clustering of colon cancer was first recognized in a family by Warthin in 1913. HNPCC is also known as the Lynch syndrome, named for Dr. Henry Lynch, a pioneer researcher in the field of cancer genetics who followed up on the original family studied by Warthin and also other families. There are two Lynch syndromes: Lynch I in which only colon cancer is passed along; and, Lynch II in which both colon and non-colon cancers (especially ovarian and uterine) are inherited.

HNPCC accounts for about five percent of colon cancer cases. The incidence of this syndrome has been controversial because until recently there has been little objective means of identifying people with the syndrome. Criteria for inclusion of cases into this syndrome were published by an International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. These three criteria are referred to as the Amsterdam Criteria: 7

The Amsterdam Criteria for Hereditary Nonpolyposis Colorectal Cancer

1.

at least three relatives have colon cancer with at least one being a relative in the immediate family

2.

two successive generations must be affected

3.

at least one individual must be diagnosed before the age of 50

Individuals with HNPCC have a strong family history of colon cancer (Lynch I) and sometimes other forms of cancer (Lynch II). Colon cancer in individuals with HNPCC look just like sporadic cases of colon cancer but the polyps that lead to colon cancer have a much more aggressive and malignant nature. Often multiple colon cancers are found, either at the same time (synchronous) or at different times in a person's life (metachronous). Greater than sixty percent of the time, cancers are found in the ascending or transverse colon (proximal to the splenic flexure).

To establish that a person has this form of colon cancer necessitates taking a careful family history to establish the genetic nature of the disorder. This obviously also has important implications for the children of a person with the disorder. The polyps found in individuals with this hereditary condition are thought to have a greater and more rapid potential for becoming malignant than those found in persons without the disorder.

Screening in family members of patients with this disorder should start at an earlier age than screening in the general population and should be done more frequently, since adenomatous polyps and cancer can reappear within six to twelve months of surgical removal. (See Chapter Nine)

Risk of colorectal cancer in the families of patients with non-hereditary adenomatous polyps. 1031 patients with adenomatous polyps in The National Polyp Study were interviewed about their family history. The risk of colon cancer in their siblings or parents was almost twice that expected, and was almost three times the rate expected when the polyps were discovered before the age of sixty.