RESUMEN
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
Asunto(s)
Predisposición Genética a la Enfermedad , Síndrome de Li-Fraumeni/genética , Sarcoma/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Femenino , Efecto Fundador , Asesoramiento Genético , Mutación de Línea Germinal , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/epidemiología , Síndrome de Li-Fraumeni/patología , Masculino , Persona de Mediana Edad , Prevalencia , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/patología , Adulto JovenRESUMEN
The identification of families at-risk for hereditary breast cancer (BC) is important because affected individuals present a much higher cancer risk than the general population. The aim of this study was to identify the most important factors associated with the presence of a pathogenic BRCA1/BRCA2 mutation. Family history (FH), histopathological and immunohistochemical characteristics were compared among BC women with pathogenic BRCA1/BRCA2 variants; VUSs in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC. The most significative differences observed concerned the molecular subtype of the tumors, age at cancer diagnosis and FH of cancer. The presence of bilateral breast cancer (BBC), number of BC cases and the presence of ovarian cancer (OC) increased (respectively) 5.797, 5.033 and 4.412 times the risk of being a BRCA1/BRCA2 mutation carrier. Besides, women with BRCA1 or BRCA2 mutations presented different tumor and FH profiles. The main characteristics associated with a BRCA1 mutation were triple negativity (OR: 17.31), BBC history (OR: 4.96) and occurrence of OC (OR: 4.32). There were no major discerning components associated with BRCA2 mutations. Thus, we conclude that tumor pathology and FH of cancer might be considered together at the time of genetic testing mainly in countries where access to genetic testing is still restricted.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Predisposición Genética a la Enfermedad , Mutación , Neoplasias Ováricas/patología , Adulto , Brasil/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , PronósticoRESUMEN
Portuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States. We identified the c.156_157insAlu BRCA2 mutation in nine (9/1,380; 0.65%) probands analised. In carrier probands, European ancestry had the highest proportion (80%), followed by the African (10%) and Amerindian and in most families with the rearrangement, haplotype analyses were compatible with the Portuguese ancestral haplotype. In conclusion, the present study reports a low albeit relevant frequency of the Portuguese BRCA2 founder mutation c.156_157insAlu in Brazilian patients at-risk for HBOC Brazilian population.
Asunto(s)
Genes BRCA2 , Pruebas Genéticas , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Pueblo Asiatico/genética , Brasil , Estudios de Cohortes , Femenino , Efecto Fundador , Tamización de Portadores Genéticos , Haplotipos , Humanos , Mutación INDEL , Población Blanca/genéticaRESUMEN
O câncer de mama é o principal câncer que atinge a população feminina no mundo, com maior taxa de incidência e mortalidade, sendo que de 5% a 10% de todos os casos são relacionados à herança de mutações genéticas. A identificação precoce dos casos de câncer de mama e ovário é importante, pois um indivíduo afetado pode herdar propriedade de antecedentes familiares que indicam uma predisposição hereditária. O efeito cancerígeno pode ocorrer quando dois genes supressores de maior importância, como BRCA1 e BRCA2, perdem suas funções nos dois alelos decorrentes de mutações na linhagem germinativa. Desta forma, foi realizada uma revisão da literatura sobre câncer de mama hereditário e suas correlações com mutações germinativas nos genes BRCA1 e BRCA2 que aumentam o risco para o desenvolvimento de câncer de mama.