Population masculine au sein des familles avec mutation germinale dans les gènes BRCA1 et BRCA2 aspects cliniques et pathologiques des cancers

Male BRCA1 or BRCA2 germline mutation carriers have an increased risk of cancer. The clinical practice shows that few men undertake genetic testing despite the actual progresses in cancer screening and treatments that may improve outcomes in men BRCA mutation carriers. A retrospective descriptive cohort study was performed to analyze the clinical and histological cancers characteristics in this population. The project consists in creating a database from information collected between 2000 and 2013 during the initial genetic counseling consultation and does not contain any updating procedure. The project cannot document the statistical cancers incidence, nor to modify the recommendations of follow-up or screening offered to the target population. During the 2000-2013 period, we identified 222 men with a known genetic status, which represent 6 % of the total male population belonging to 282 families with hereditary breast and ovarian cancer and with members harboring a deleterious or suspect deleterious mutation in BRCA1 or BRCA2 genes. We also noticed that the index case, the first individual tested because of a personal and family cancer history and who allowed the identification of the familial mutation, was a man in 1,5% of the studied families. This cohort included 142 mutation carriers: 62 with a BRCA1 mutation, 79 with a BRCA2 mutation, a double heterozygosity for BRCA1 and BRCA2 mutations in one (01) case and 80 noncarriers.  The majority (95%) are a French-Canadian descent and born between 1904 and 1992.  Two mutations commonly reported in the French-Canadian founder population: c.4327C>T (4446C>T) in BRCA1 and c.8537_8538delAG (8765delAG) in BRCA2 were the most frequently identified (43%) in our study. Up to 37% (52/142) of men BRCA mutation carrier had a cancer of which ten (10) had two different cancers. Unsurprisingly, the proportion of cancers was more frequent in the mutation carrier group vs non-carrier (p˂0,001) more over this proportion was greater in the BRCA2 mutation carriers group when compared to the BRCA1 mutation carriers (0,016). We did not find a difference in the age of diagnosis between groups.  Prostate cancer was the most frequent with 20 cases, the mean age at diagnosis was 62 years old and it consists mainly of an adenocarcinoma type with high Gleason score (greater than 7). Breast cancer is rare in male population, it is the second most common cancer in our cohort with 12 cases. It was associated with BRCA2 mutation (p = 0,009). The mean age at diagnosis was 62 years old. The invasive carcinoma was the most frequent type with positive hormonal receptors status.  We identified 14 other cancers types: skin (06), lung (04), colorectal (03), pancreas (03), lymphoma (02), bone marrow (02), testis (02), Adrenocortical carcinoma (01), stomach (01), hypopharynx (01), tongue (01), bone (01), kidney (01), thyroid (01) and in two (02) cases it was metastatic with unknown primitive site.  Male BRCA1 or BRCA2 germline mutation carriers need a long-term follow-up for cancer screening and use of the appropriate treatments. Unfortunately, only a small number of men have undergone genetic testing.  The key solution is probably in sensitising to this issue as well healthcare professionals as members of the BRCA1 or BRCA2 mutation carriers families. The results of the present study will serve as basis to estimate the progress realized in the follow-up of this population in the future studies.

Keyphrases: Mutation, BRCA1, BRCA2, Cas-index, Cancers, Men, Cohort study, French-Canadian, Mutation carrier, Index case