A Review of Hereditary Colorectal Cancers

Excerpt

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer-related deaths in the United States. CRC is the leading cause of cancer deaths in men aged 50 or younger and the second leading cause in women of the same age group, following breast cancer. CRC is almost always preceded by adenomatous or serrated colon polyps. About 65% of CRC cases are sporadic, 25% are associated with a family history of CRC or adenomatous polyps in first-degree relatives, and the remaining 10% are attributed to hereditary (genetic) CRC syndromes.

The risk of CRC is approximately twice as high in individuals with a family history of CRC compared to those without such a history. Hereditary CRC syndromes result from specific genetic mutations that increase susceptibility to CRC, as well as other malignancies and benign conditions. Familial adenomatous polyposis (FAP) and Lynch syndrome, also referred to as hereditary nonpolyposis CRC (HNPCC), are the most prevalent hereditary CRC syndromes. These conditions are generally more aggressive, have a poorer prognosis, and may be less responsive to chemotherapy compared to sporadic CRC.

A genetic or hereditary cause of CRC should be suspected and investigated if one or more of the following factors are present:

1. A significant family history of CRC or premalignant colon polyps in 2 or more first-degree relatives of the proband.

2. A family history of other cancers known to be associated with hereditary CRC, particularly endometrial cancer.

3. Onset of CRC at an unusually early age.

4. Multiple primary cancers in an individual, including CRC.