Distribution of BRCA1 and BRCA2 Mutations in Asian Patients with Breast Cancer / 한국유방암학회지

Breast cancer is the most prevalent cancer in Asian females, and the incidence of breast cancer has been increasing in Asia. Because Asian patients develop breast cancer at a younger age than their Caucasian counterparts, the contributions of BRCA1 and BRCA2 (BRCA1/2) mutations in Asians are expected to be different than in Caucasians. The prevalence of BRCA1/2 mutations in the Asian population varies among countries and studies. Most Asian studies have reported more frequent mutations in BRCA2 than in BRCA1, with the exception of studies from India and Pakistan. In addition, the contribution of large genomic rearrangements of BRCA1/2 genes is relatively small in Asian populations in comparison to other ethnic populations. Various statistical models for the prediction of BRCA1/2 mutations have underestimated the risk of having these genetic mutations in Asians, especially in predicting BRCA2 gene mutation. Until recently, BRCA1/2 mutation analyses in Asia were mostly conducted by independent single institutions with different patient selection criteria and using various genotyping methods. However, a couple of Asian groups have initiated nationwide studies collecting BRCA1/2 mutational data. These national collaborative studies will help a comprehensive understanding of the prevalence of BRCA1/2 mutations in the Asian population.

BRCA1 and BRCA2mutations in breast cancer patients from Venezuela

A sample of 58 familial breast cancer patients from Venezuela were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIM no. 113705) and BRCA2 (MIM no. 600185) genes by using conformation-sensitive gel electrophoresis. Ashkenazi Jewish founder mutations were not found in any of the samples. We identified 6 (10.3%) and 4 (6.9%) patients carrying germline mutations in BRCA1 and BRCA2, respectively. Four pathogenic mutations were found in BRCA1, one is a novel mutation (c.951_952insA), while the other three had been previously reported (c.1129_1135insA, c.4603G>T and IVS20+1G>A). We also found 4 pathogenic mutations in BRCA2, two novel mutations (c.2732_2733insA and c.3870_3873delG) and two that have been already reported (c.3036_3039delACAA and c.6024_6025_delTA). In addition, 17 variants of unknown significance (6 BRCA1 variants and 11 BRCA2 variants), 5 BRCA2 variants with no clinical importance and 22 polymorphisms (12 in BRCA1 and10 in BRCA2) were also identified. This is the first genetic study on BRCA gene mutations conducted in breast cancer patients from Venezuela. The ethnicity of our population, as well as the heterogeneous and broad spectrum of BRCA genes mutations, must be considered to optimize genetic counseling and disease prevention in affected families.

A contribuição dos genes BRCA na predisposição hereditária ao câncer de mama / BRCA genes contribution in the hereditary predisposition for breast cancer

Aproximadamente 20 % dos casos de câncer de mama familiar estão associados a um dos genes de susceptibilidade hereditária para câncer de mama e ovário, BRCA1 e BRCA2. Recentes trabalhos têm demonstrado o mecanismo de ação destes genes com funções estabelecidas na manutenção da integridade do genoma e no controle da recombinação homóloga. A história familiar, a bilateralidade, o acometimento precoce e achados histopatológicos específicos são fatores sugestivos da presença de mutações nestes genes. Esta revisão sumariza alguns destes conhecimentos, na tentativa de colocá-los no contexto atual das funções destes genes.

Approximately 20% of the cases related to familiar breast cancer are associated to one gene of hereditary susceptibilityfor breast and ovarian cancer, BRCA1 and BRCA2. Recent works have demonstrated the mechanism of action of these genes, with functions well established for maintaining the genome integrity and for controlling homologatesrecombination. Familiar history, bilaterality, precocious diseases, as well as specific histopathologic results areindicative factors of the presence of mutation in these genes. This literature review summarizes some of thisknowledge, trying to understand them in the current functional context of these genes.