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Colorectal Cancer

Colorectal cancer also known as colon cancer or bowel cancer is the fourth most prevalent cancer and the second largest cause of cancer mortality in the western world. It is also one of the most curable cancers when identified early1. In the USA only 39% of colorectal cancers are detected early, at a localised and often symptomless stage when the five year survival rate is 90%2. This highlights the importance of colorectal cancer screening.

Most colon cancers develop from benign polyps on the surface of the colon. Risk factors include:

With many of the risk factors being hereditary genetic screening for predisposed mutations can enable the early detection and therefore treatment of colorectal cancers.

Many colorectal cancers are the result of several mutations in the tumour suppressor genes and proto-oncogenes over a period of years. Some of the main genes involved are listed below:

APC Tumour Suppressor Gene - Mutation of the APC tumour suppressor gene is often the earliest identifiable event in colorectal carcinogenesis. Loss of function of the APC protein deregulates ß-catenin resulting in the stimulation of cell proliferation. All daughter cells carry the APC mutation.

K-ras and BRAF - Point mutations in the oncogenes K-ras or BRAF permanently activate the proteins involved in the transduction of extracellular growth signals. Continuous signals from cell surface receptors to the nucleus allow progression to adenoma.

TP53 Tumour suppressor gene- Inactivating mutations of the TP53 tumour suppressor gene can trigger the transition to malignant cancer by preventing cell cycle arrest or apoptosis in response to DNA damage.

Screening is important to detect cancer before the onset of symptoms increasing the chances of survival. At present current screening methods include;

Faecal DNA testing is a non invasive method allowing the identification of the mutations associated with colorectal cancer resulting in earlier detection and better patient prognosis. The Ranplex CRC assay utilises this method and is suitable for detecting mutation in the genes listed above.

1.Toribara NW and Sleisenger MH. (1995) Screening for colorectal cancer. N Engl Med 332(13):861-7
2. Fearon ER and Vogelstein B. (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759-67.

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