Colon cancer family history: A family history of colorectal cancer (CRC). First-degree relatives of people with CRC are themselves at a 2 to 3-fold increased risk of colorectal cancer. (Parents, brothers and sisters, and children are first-degree relatives.) When the family history includes 2 or more relatives with CRC, the possibility of an inherited CRC syndrome is increased.
A detailed family history needs to be taken, ideally in pedigree form, to determine the number of relatives affected with CRC, their relationship to the patient, the age at which the CRC was diagnosed, the presence of multiple primary CRCs, and the presence of any other cancers in the family consistent with the presence of an inherited CRC syndrome.
The following empiric risk figures are commonly used in genetic counseling for colorectal cancer (CRC):
If there is no family history of CRC, the risk of developing CRC by age 79 is 4%.
If there is one first-degree relative with CRC, the risk of developing CRC by age 79 is 9% and the relative risk of CRC is 2.3 times that of someone with no family history of CRC.
If there is more than one first-degree relative with CRC, the risk of developing CRC by age 79 is 16% and the relative risk of CRC is 4.3 times that of someone with no family history of CRC.
If there is one affected first-degree relative diagnosed with CRC before age 45, the risk of developing CRC by age 79 is 15% and the relative risk of CRC is 3.9 times that of someone with no family history of CRC.
If there is one first-degree relative with colorectal adenoma (a polyp), the risk of developing CRC by age 79 is 8% and the relative risk of CRC is 2 times that of someone with no family history of CRC.
A number of genes that govern the risk of CRC have been identified. The large majority of them are inherited in an autosomal dominant manner. Family history features suggesting autosomal dominant inheritance include the following: vertical transmission of cancer predisposition from generation to generation; a risk of 50% for each child born to someone with the cancer predisposition; and both males and females affected. Features consistent with an inherited predisposition to cancer include tumor diagnosis at an younger age than in sporadic cases (those without a family history); a predisposition to different cancers such as CRC and endometrial cancer; and the occurrence of 2 or more primary cancers in a single individual.
There are several autosomal dominant forms of CRC. These include familial adenomatous polyposis (FAP) and an attenuated form of polyposis (AFAP) and hereditary nonpolyposis colorectal cancer (HNPCC). FAP and AFAP are both due to germline mutations in the APC gene whereas HNPCC is due to germline mutations in mismatch repair (MMR) genes.
There are also many other families that have an unusual number of relatives with adenomas (polyps) or CRC but that do not appear to have a known inherited CRC syndrome. These kindreds are collectively said to have familial colorectal cancer (FCC).
The accuracy and completeness of the family history must be taken into account in using it to calculate the risk of CRC. The family may contain members who are thought to have had CRC but who did not in reality have it. Conversely, the family may be unaware of relatives with CRC or other forms of cancer. Small family size is common today and may limit how informative a family history may be. Some persons may carry an autosomal dominant predisposition to CRC but not develop cancer, giving the mistaken impression of “skipped” generations in the family history. And at least one form of CRC is inherited in an autosomal recessive manner and the risk is usually limited to one sibship within a family.
However, when family histories of colon cancer were checked in a research study, a sensitivity of 73% was obtained. This indicates that what people tell about their family histories is a reasonably good indicator of their actual family history.
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