Susceptibility to cancer has long been recognised thanks to the observation of familial cancers but the identification of genes implicated in the disease is an area that is still evolving.
This program studies genes susceptible to cancer but also the germline determinants of cancer prognosis and treatment responses in terms of sensitivity and toxicity.
Predisposition and risk factors : study by organ or by concept
1) Predisposition to breast and ovarian cancer
Project coordinated by Dr Nadine Andrieu (Inserm / IC) and Dr Catherine Noguès (IC)
- Better estimation of tumour risks in women carrying the mutations linked with familial breast and ovarian cancers (BRCA1 and BRCA2 mutations and the ATM gene responsible for Ataxie-Telangiectasie)
- Identification of new inherited susceptibility factors
- Estimation of cancer risks associated with the ATM heterozygosity gene
The establishment of major international studies is essential in obtaining sufficient statistical power. This project is in part based on large international cohorts (see right-hand column: participation in the development of cohorts and consortium).
2) Developmental abnormalities, DNA repair defects and tumour risks
Project coordinated by Dr Franck Bourdeaut (IC) and Dr Marc-Henri Stern (Inserm / IC)
The goal of this project is to identify susceptibility factors based on the study of 2 groups of patients presenting hereditary characteristics with multiple points in common: developmental abnormalities and DNA repair defects. The project is organised around 3 axes:
- Identification of predisposing genes based on a cohort of patients with both tumours and developmental abnormalities (TED cohort, Tumour and Development)
- Identification of genomic and functional markers of DNA double strand break repair defects at the germline and tumour levels.
- Developing NGS approaches to identify new predisposing genes.
3) Prognostic or treatment response biomarkers
Project coordinated by Dr Claude Houdayer (IC)
The germline genetic component is well established in the ethiology of numerous cancers. Furthermore growing evidence suggests that genetic traits influence the prognosis and response to treatment. This project aims to identify new germline genetic factors that can be used in the clinic as prognostic and predictive biomarkers of the effects of radiation therapy.
Diagnostic and prognostic advances
Identification of a "BRCAness" signature highlighting a double strand break repair defect in tumours inactivated for BRCA1/2 or BRCA-like genes (Popova et al, Cancer Res, 2012).
Incidence, presentation and prognosis of malignant tumors in patients with ataxia-telangiectasia; (Suarez et al, J Clin Oncol, 2015)
- Establishment of an institutional consent form for non-interventional studies
- Setting up of a Genetic and Epidemiologic Investigation Platform (PIGE), see the PIGE block in the right hand column for more information