As cancer has a strong genetic basis, genetic screening should potentially have 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 them to know what their chances are of developing a disease (Strachan and Read, 1999). Screening can also allow potential parents to know what the likelihood is of any future offspring developing the condition. Unfortunately, in cancer studies screening is not so 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 (Ponder, 2001). 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 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 most common cancer syndrome screened for is familial breast and ovarian cancer caused by the genes BRCA-1 and BRCA-2, and many clinical cancer centres as well as private companies now offer screening for BRCA-1 and BRCA-2 mutations in families with multiple cases of these tumours (Foster et al., 2002). 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, Eisen and Weber, 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 administering drugs that reduce the chances of developing 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 it is possible there are many genetic risk factors yet to be discovered (Balmain, 2001).
Genes that confer strong susceptibility to other familial cancers are also starting to be screened for in a similar manner. Genetic testing can now be used to confirm diagnosis or to predict disease development in families potentially affected by the many of the better-studied but relatively rare cancer syndromes (e.g. retinoblas-toma, Li-Fraumeni syndrome and Von Hippel-Lindau syndrome) which are caused by single gene defects and have clear patterns of inheritance (Hampel et al., 2004). Screening programmes are being developed and starting to be offered commercially and by some hospitals for other useful genes strongly involved in more general familial cancer syndromes. These include thep16Ink4a gene in familial skin melanoma, and the various tumour-suppressor and DNA-repair genes involved in the familial colon cancer syndromes, such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC). These genes significantly increase the risk of getting the cancer and detection of these mutations indicates that better surveillance and/or the deployment of early prophylactic measures may be appropriate (Rogowski, 2006).
Was this article helpful?