Colon Cancer Genes

The major genes of colon cancer are identified with linkage analysis of genes obtained from high risk families. They are those families where a lot of family members are suffering from colorectal cancer. There are only a small number of colon cancers (5-10%) that can be linked directly to these genes, and thus considered a genetic disease.

There are three major classes of colon cancer genes: oncogenes, tumor suppressor genes and stability genes.

Although somatic mutations of oncogenes are frequently found for colon cancer, germline mutations of these genes do not appear to contribute to inherited colon cancer. Mutations of oncogenes such as KIT and PDGFRA have been shown to cause Familial GI Stromal Tumor.

On the other hand, tumor suppressor genes are thought to be responsible for hereditary cancer syndromes, familial adenomatous polyposis (FAP) and juvenile polyposis.For instance, the adenomatous polyposis coli gene (APC) is often referred to as the gene directly responsible for colon cancer. APC is involved in many important cellular functions including cell adhesion, migration, signal transduction, and apotosis. Germline mutations of APC lead to FAP. Patients having FAP tend to develop multiple polyps as early as 15-20 years old and cancer as early as 40 years old. Somatic mutations of APC are present in most if not all sporadic colon cancers.

Stability genes contribute to a significant fraction of hereditary colorectal cancers. Stability genes such as hMLH1, hMSH2 and hMSH6 have been linked to Hereditary Nonpolyposis Colon Cancer (HNPCC) or commonly known as Lynch syndrome. Patients with HNPCC have 70-80% chance of developing colorectal cancer by the age of 70. hMLH1, hMSH2 and hMSH6 are also known as mismatch repair genes.These are responsible for making proteins which correct mispairing of DNA nucleotide bases and miscellaneous insertions or deletions during DNA replication. In other words, these genes maintain the fidelity of DNA replication.

In fact, testing for mutations of hMSH2 and hMSH6 is the basic for genetic screening for Lynch syndrome. Another stability gene associated with colon cancer is MYH. MYH is responsible for correcting oxidative DNA damages.

National Cancer Institute: Colon cancer genes

Colaris: A Genetic Test for HNPCC