Genetic screening of cancer

As cancer has a strong genetic basis, genetic screening should have potential applications for determining prognostic information. In classic monogenic (one-gene) familial genetic disorders such as Huntington's disease, screening of potentially affected family members can allow people to know what their chances are of developing a disease. Screening can also allow potential parents to know what the likelihood is of any future offspring developing the condition. Unfortunately in cancer studies this is not as straightforward, as a result of the complexity of cancer genetics. Inherited cancer syndromes that act similarly to classic genetic diseases cause only about 1% of human cancer. A further 5-10% of all cancers (depending on how strictly defined) have a more general familial basis (Ponder, 2001). In these families several cases of common cancers are found, usually falling into general groups of cancers (e.g. breast and ovary, or colon, endometrium and urinary). Only these rarer familial cancers have a potential requirement for genetic screening. If the risk to a family member can be determined, there is a possibility that preventive steps can be taken.

So far, the only major familial cancer screened for is familial breast and ovarian cancer caused by the genes BRCA-l and BRCA-2. Some cancer centres now offer screening for BRCA-1 and BRCA-2 mutations in families with multiple cases of these tumours. If mutations are found it is estimated that a woman has up to an 85% lifetime risk of developing breast cancer and a 60% risk of developing ovarian cancer (Armstrong et al., 2000). If BRCA mutations are detected, intensive monitoring can be used to pick up developing tumours at an early stage. For the most high-risk cases preventive measures such as prophylatic mastectomy, or taking drugs that reduce the chances of these cancers (such as tamoxifen), can be considered. Unfortunately BRCA-1 and BRCA-2 mutation-associated familial cases account for only around 15-20% of familial cancers, so possibly there are many genetic risk factors yet to be discovered (Balmain, 2001). Genes that confer strong susceptibility to other familial cancers may eventually be screened in a similar manner. Useful genes for which screening programmes may be developed could include the pi6[nk^a gene in familial skin melanoma, and the various tumour suppressor and DNA-repair genes involved in the familial colon cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC).

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