Genetic Epidemiology of Cancer

Projects developed by the Genetic Epidemiology of Cancer Team (GEC) aim at characterizing genetic variants involved in familial cancers by considering effects of other genetic or non-genetic factors. In addition to variants involved in monogenic transmission, variants involved in polygenic modes of cancer inheritance are also studied, as well as their interactions with lifestyle and environmental exposures. Results from this research will in fine allow to improve risk prediction models and therefore to more precisely estimate tumor risks, which in turn will help elaborating personalized screening, follow up and new prevention strategies.

Studied populations are populations at high risk of cancer, such as Hereditary Breast and Ovary Cancer (HBOC) families, or populations having a cancer risk a priori similar to that of the general population, as in studies conducted on differentiated thyroid cancers, cancers of the digestive tracts or melanoma.

Current research on cancer-prone families focuses on pathogenic or predicted pathogenic variants in high- to moderate-risk genes such BRCA1, BRCA2, PALB2, CHEK2 and ATM, as well as on variants in other genes generally included in HBOC multigene panels, but for which the clinical utility of genetic testing still needs to be assessed. Another objective of GEC is to identify new inherited genetic factors in women with no identified pathogenic variant in the known breast cancer susceptibility genes.

To address these research questions, GEC uses multidisciplinary approaches (epidemiology, molecular genetics, biostatistics, bioinformatics) integrating data from genetics, epidemiology, clinics, high-throughput genotyping and sequencing data, as well as tumors characteristics.

Within the Team, the Platform of Investigation in Genetics and Epidemiology (PIGE) was established to support epidemiology- and genomics-related activities. The PIGE is involved in the setting up, collection and centralization of epidemiological, familial and clinical data of the national studies that we coordinate. Specifically, the PIGE participates in the development of protocols (study strategy, power calculations, logistics, etc.) and is in charge of the administrative and legal processes related to studies, organizes logistics, edits various documents (information notices and informed consent forms, questionnaires, etc.) and develops and updates the databases of each study. As examples, the PIGE is in charge of the collection and management of data of GENESIS (study on sib pairs affected with breast cancer and with no BRCA1/2 mutation), CoF-AT2 (prospective cohort of families segregating an ATM variant, including ataxia-telangiectasia families and cancer-prone families) and TUMOSPEC (nation-wide family-based study to assess cancer risks in families with a predicted pathogenic variant identified through HBOC multi-gene panel testing and to determine their associated tumor spectrum).

GEC also aims to adapt laboratory, pathology and bioinformatics-related genomic techniques to suit GEC projects’ particular needs and is endowed with a wet lab activity. Biorepositories and sample management of the GENESIS and CoF-AT2 studies, as well as of GEMO (Genetic modifiers of BRCA1/2), a DNA bank of BRCA1/2 mutation carriers established to study genetic modifiers of BRCA1 and BRCA2, are also handled in our laboratory.

The Team has established collaborations with a number of other international teams and contributes to projects conducted in the framework of several consortia, including CIMBA (Consortium of Investigators of Modifiers of BRCA1/2), BCAC (Breast Cancer Association Consortium), IBCCS (International BRCA1/2 Carriers Study), ENIGMA (Evidenced-based for the Interpretation of Germline Mutant Alleles) and EPITHYR (EPIdemiology of THYRoid cancers).