About 5 to 10 % of certain types of cancer occur where a hereditary predisposition exists (JCO Precision Oncology 2017 :1, 1-12; Gut 2017;66:464–472).

This derives from a loss of function of a gene that acts as a tumour suppressor, normally preventing the formation of cancer. Carriers of predispositions therefore develop different cancers more often and earlier than the general population and pass this predisposition on to some of their offspring (typically 50% probability).

Typical examples of hereditary predispositions to cancer are those caused by mutations in the BRCA1 and BRCA2 genes, responsible for breast and ovarian cancers, and also by mutations in MMR genes, which greatly increase the risks of developing colon and endometrial cancers.

The critical issue is to identify the greatest number of carriers early enough to put in place preventive and monitoring measures. The ultimate goal is to reduce morbidity and mortality associated with these cancers, to screen relatives for the same purpose, and to offer reproductive diagnostic options to prevent transmission of the predisposition.

A more recent idea involves targeted therapies that can benefit predisposition carriers.

For example, PARP inhibitors (a family of proteins that repair single-strand breaks in DNA) instigate selective suicide of cancer cells in carriers of the mutation (a concept known as synthetic lethality). In the absence of PARP activity due to targeted therapy and in the presence of BRCA mutations, programmed cancer cell death is triggered.

This therapy has proved to be very effective in advanced ovarian and breast cancers, but also for forms of pancreatic and prostate cancers resistant to other treatments.

An equivalent mechanism also applies to BRCA mutations that are limited to the tumour (somatic mutations), and more generally to all mutations causing homologous recombination deficiency (HRD) in the tumour. MMR deficiency may also qualify patients for targeted therapy (immunotherapy).

In practice, our genetics counsellors and oncogenetics specialists associated with breast centres and other cancer centres are at your disposal to manage your patients and prescribe these tests.

Any cancer that occurs in several members of a family and/or one or more cancers that appear before the age of 50 merit assessment, for which we are entirely at your disposal.

Predispositions to cancers that have a multifactorial basis are discussed in the chapter "genetic predispositions".

Cancer screenings / BRCA1 and BRCA2 genes