Cancer is a very heterogeneous disease, resulting from accumulation of mutations in the DNA. The etiology of cancer is multifactorial, involving genetic, environmental and other medical factors as well as lifestyle factors that interact to develop a specific malignancy.
About 5% -10% of cancers are hereditary and genetic testing has been used for certain hereditary forms of cancer for more than a decade.
The knowledge of the genetics of cancer improves rapidly with the understanding of the molecular mechanisms, which help to identify individuals at high risk, enables characterization of the disease, allows for customized treatments adapted to the molecular basis of the disease, and leading to the development of new therapies.
This expansion of knowledge has implications for all aspects of cancer management, including prevention, detection and treatment.
The percentage of people carrying a pathogenic mutation and who will eventually develop the disease is referred to as penetrance.
Generally, common genetic variants-mutations associated with a predisposition to cancer have a low penetrance compared to rare pathogenic mutations. The precise identification of individuals and families, who are at increased risk of developing cancer, is an important purpose of primary health care.
Once these individuals are identified, they can be evaluated further, through appropriate genetic counseling, in relation to the risks and the required genetic testing, which will lead to the implementation of a personalized management strategy.
Until recently, the most widely used method for the genetic testing of hereditary cancers was the analysis by Sanger DNA sequencing, which is considered the ‘golden standard’ for detecting mutations.
Nevertheless, because the genes associated with hereditary forms of cancer are very large and there are no specific mutation hot spots, this traditional method has generally proven to be time consuming, costly and with a moderate to low diagnostic yield .
