Hereditary Nonpolyposis Colorectal Cancer

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Bharati Bapat, PhD, Department of Pathology, Molecular Diagnostic Laboratory

Colorectal cancer is the third most common cancer in Canada. some cases of colon cancer are hereditary, that is, a family history in such cases reveals that each child of an affected parent has a 50 percent risk of the disorder. Such information is stored in a miraculous substance, DNA, which is rapidly becoming the key of modern medicine, especially medicine dealing with inherited diseases.

In all cells in our body, DNA, short for deoxyribonucleic acid, is organized on 23 pairs of chromosome. One member of each pair is contributed by each parent. These chromosomes are numbered from 1 to 22, according to their size. The 23rd pair is the sex chromosome. Hereditary informaion regarding the colour of or hair or eyes, as well as other traits that we may inherit from our parents, is stored in the form of small DNA subunits called genes which are organized on chromosomes. In our bodies, several thousand genese exist and control every process that human cells perform. Faulty genese cause diseases and in the case of hereditary nonpolyposis colorectal cancer, such faulty genes are passed on from one generation to another. Many researchers around the world have been collecting information regarding family members from patients with colon cancer spanning previous generations.

If the family history identifies three people with colon cancer in two successive generations and at least one of them was diagnosed under age 50 years, then such cases are considered hereditary or familial. Unlike another inherited bowel disease, familial polyposis, there are no early clues except for the family history of cancer. In such families, approximately 2-3 tablespoons of blood are collected from the affected person, spouse, children, and siblings. DNA is then extracted and analyzed to find the location of the faulty gene on a specific chromosome, using a technique called DNA linkage analysis.

With this approach, scientists from Johns Hopkins Hospital in Baltimore, Maryland, and the University of Helsinki, Finland, were able to examine many large families with colon cancer. It appears that different forms of hereditary colon cancer exist and are caused by different genes. For example, in some families, the culprit is a faulty gene on chromosome 2. In the near future, it will be possible to devise a simple blood test for these particular families to decide who is at high or low risk of inheriting the colon cancer gene from their parent.

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