Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
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.
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.