IMoST - Hereditary predisposition to cancer

Published on October 3, 2024 – Updated on October 3, 2024

Hereditary predisposition to cancer is characterized by a constitutional pathogenic gene variation, and has two main consequences: people carrying these mutations are exposed to a higher risk of cancer than the general population, and there is a risk of the mutation being passed on to offspring.

Hereditary predisposition to cancer is characterized by a constitutional pathogenic gene variation, and has two main consequences:

• Individuals carrying these mutations are at a higher risk of cancer compared to the general population. This risk varies depending on the gene involved.

• The risk of transmitting the mutation is 50% for each descendant and the associated hereditary predisposition follows an autosomal dominant mode of transmission.

Identifying the molecular causes of such a predisposition in a patient allows to offer appropriate screening and prevention measures, as well as familial genetic exploration. Genetic analysis of the family helps to determine relatives at risk and thus adapt their follow-up within the framework of personalized medicine. It also reassures and reduces the follow-up of relatives who do not carry the genetic predisposition.

However, depending on the tumor locations, the genes identified today only explain 5 to 20% of familial cancers through monogenic hereditary predisposition. Our group has therefore implemented different approaches to understand the unexplained causes of hereditary predisposition:

• We are searching for new predisposition genes through the exomic analysis of particularly evocative families.

• In the specific case of breast cancer, we are working to enrich knowledge on moderate penetrance genes, for which management is not consensual yet. A particular focus is on the CHEK2 kinase.

• The absence of a monogenic cause may also indicate a polygenic predisposition. Some assessment tools exist but they have not yet reached maturity, and we are developing approaches to assess the relevance of these polygenic risk scores in clinical practice.

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