Colorectal cancer (bowel cancer) is a common type of cancer and affects about 1 in 25 people. For most individuals it is a disease of old age and occurs by chance. Probably about 5-10% of bowel cancer is caused by an inherited predisposition. When it is inherited bowel cancer occurs at a younger age and several people in a family can be affected. There is no obvious hereditary trait in most people with colon cancer. There are 3 broad types of inherited bowel cancer:
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
- Familial Adenomatous Polyposis (FAP)
- MYH-Associated Polyposis (MAP)
Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
HNPCC is an inherited condition characterised by the early onset of colorectal cancer and it accounts for approximately 2-3% of all colorectal cancers. It is also associated with the frequent occurrence of other cancers arising from the uterus, ovaries, stomach or upper gastrointestinal tract.
Regular screening is offered to individuals in an HNPCC family. Regular colonoscopy is offered for detailed examination of the colon, and if polyps are found they can be removed before they can become cancers. Other screening may be offered when there are other types of cancer in the family, such as endometrial, stomach or ovarian.
In some families, where there is an increased susceptibility to colorectal cancer we can identify a fault in either of the known bowel cancer genes. The three main genes involved in bowel cancer are MLH1, MSH2 and MSH6 There are many other genes not yet identified which may contribute towards bowel cancer. It may be possible to find families who are most likely to carry an alteration in one of these bowel cancer genes by doing genetic analysis on tumour tissue, compared with a blood sample, to look for the genetic instability which is characteristic of the known genes.
If such a gene fault is identified it allows us to offer a blood test to other family members to see whether or not they have inherited the same faulty gene. A person who has inherited the fault will be at high risk of developing bowel cancer in their lifetime. They will be offered bowel screening by colonoscopy every 2 years, and may be offered other forms of surveillance depending on the family history. However, we know that not everyone with the inherited gene fault does ultimately develop cancer. A person who is found not to have inherited the faulty MLH1 or MSH2 gene in their family will no longer be considered to be at high risk of developing bowel cancer, and their children will not need testing.
Having a blood test to see whether or not a person is at high risk of developing cancer is not something which should be entered into without a lot of thought about the implications of the result of the test.
Some protective factors have been identified in bowel cancer. A diet high in fruit and vegetables, moderate alcohol consumption, not smoking and regular exercise may reduce the risk of bowel cancer.
Familial Adenomatous Polyposis (FAP)
FAP is an inherited disorder that accounts for about 0.5% of all the cases of colorectal cancer. It is characterised by the appearance of many polyps in the bowel. In individuals with FAP, colorectal cancer often develops in untreated cases by about the fourth decade, 20-30 years younger than non-familial colon cancer. Polyps can also occur elsewhere in the gastrointestinal tract and extra-intestinal lesions can develop in some individuals.
The gene which causes FAP is known (APC) and faults in this gene can be identified in most affected families. Therefore for many families, a genetic test is possible to tell which relatives are at risk and need to be monitored, and which can be reassured that they are not at risk.
Close relatives of somebody affected with FAP have a 50% risk of inheriting the gene. They would be offered bowel examinations starting from 10 - 15 years of age to detect polyps, so that treatment can be offered before a bowel cancer develops.
In some families, the gene behaves differently and there are fewer polyps with a later age of onset. This is called Attenuated FAP, but is inherited in the same way and the bowel cancer risks remain high.
MYH-Associated Polyposis (MAP)
In other families, a different gene is involved called ‘MYH’. With this condition, MYH associated polyposis, the gene behaves as an autosomal recessive (rather than autosomal dominant as in HNPCC and FAP) and affected individuals have 2 copies of the gene fault, one from each parent. Carriers who have only 1 abnormal copy do not have an increased risk of developing polyps, and the main risks in the family are to brothers and sisters rather than to children. Since just two common gene mutations underlie most cases of MYH polyposis, it is relatively easy to confirm the diagnosis on genetic testing.