Hereditary Breast and Ovarian Cancer, Mutation
Conditions
Keywords
Oncogeneticists, Mutations, Breast Cancer, Ovarian cancer
Brief summary
TUMOSPEC is a national family study designed to measure the relative and absolute risk of cancer for carriers of deleterious mutations to these "new" breast cancer (BC) susceptibility genes. Index cases will be enrolled consecutively from patients attending an appointment at one of the Unicancer centres, with no other inclusion criteria, and offered a BRCA1/2 analysis as part of their care plan. A panel of 24 TUMOSPEC genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study. If a mutation is found, the index cases will be asked to invite their first and second degree family members and their cousins to take part in the study, regardless of whether they have cancer. Saliva samples will be then taken and used for a targeted analysis of the familial abnormality. Each participant will also complete an epidemiological questionnaire in order to gather information about his/her medical history and any exposure to various risk factors. All medical and genotype data will be centralised at the Genetic Epidemiology Research Platform (PIGE, INSERM). The cumulative mutation frequency for all genes is estimated at 10%. Penetrance will be analysed using methods designed to minimise selection bias. The expression spectrum of the mutations will also be described. For genes where the number of mutated families is too low, the data may be contributed to international consortia. The main project will be preceded by a two-year feasibility study, using the same inclusion criteria and logistic circuits. It is this pilot study to which the current funding application relates.
Interventions
OTHERGenetic testing
A panel of 24 genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study.
Sponsors
UNICANCER
Institut Curie
Gustave Roussy, Cancer Campus, Grand Paris
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Index case eligibility: Any person with an indication for a BRCA1/BRCA2 gene analysis and who has been offered TUMOSPEC panel screening. Age ≥18 years. Family member eligibility: Family members will be eligible if the mutation identified in the Index Case is considered deleterious. Any family member to the first and second decree or a cousin of the Index Case. Family members from both sides of the family will be invited to take part. Age ≥18 years.
Exclusion criteria
People deprived of their civil liberties or who are under judicial protection or guardianship. Patients unable to answer the questionnaire for social or psychological reasons. Children of the index cases, of any age.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Penetrance estimation of the mutations identified in the gene panel | 2 years | The primary outcome is to obtain unbiased penetrance estimates of the mutations identified in the gene panel (about 20 genes), which will be analysed by the molecular diagnostic laboratories at the same time as the BRCA1 and BRCA2 genes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The results for the whole panel sequencing will be formatted to be used by all laboratories allowing the subsequent centralisation of the data. | 2 years | This outcome will allow to establish a procedure for centralising homogeneous genomic sequencing data produced by the molecular diagnostics laboratories |
| Relative risk will be determined by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene. | 2 years | To determine the deleterious nature of a variant the gene panels will be analysed by the various molecular diagnostics laboratories and we will estimate the relative risk by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATOROlivier CARON, MD
Gustave Roussy, Villejuif, France
PRINCIPAL_INVESTIGATORAndrieu Nadine, PhD
Institut Curie, Paris, France
PRINCIPAL_INVESTIGATORSeverine Eon Marchais, PhD
PIGE Institut Curie, Paris, France
Outcome results
None listed