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American Association for Cancer Research, Cancer Research, 9_Supplement(75), p. P4-13-02-P4-13-02, 2015

DOI: 10.1158/1538-7445.sabcs14-p4-13-02

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Abstract P4-13-02: BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil

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This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Abstract Background: Genetic susceptibility to Hereditary Breast and Ovarian Cancer (HBOC) syndrome could be test by the screening of BRCA1 and BRCA2 genes. Thus, knowing that each population has its degree of heterogeneity and the Brazilian population is one of the most heterogeneous of the world, we aimed to verify the frequency of BRCA1/2 founder mutations in high-risk HBOC patients from Bahia, the biggest State of the Northeast of Brazil. Methods: It was analyzed the DNA of 98 unrelated high-risk HBOC patients, considering the criteria of NCCN v.1.2010. These patients were tested for the next founder mutations: BRCA1 c.211A>G (Galician), BRCA1 943ins10 (African), BRCA1 3450del4 (Hispanic) and BRCA2 c.5946_5946delT (Portuguese) by sequencing or PCR/RFLP. All positive results were confirmed by two sequencing reactions. The genetic ancestry was analyzed with a panel of 10 ancestry informative markers (AIMs). The clinical and epidemiological data were collected during the genetic counseling and were analyzed in Epi InfoTM 7, while the frequency of the AIMs was analyzed in GENEPOP, and in ADMIX95 the genetic admixture was estimated. Results: All patients had personal and/or familial history of breast and/or ovarian cancer. Most of the patients self-reported as mulatto (61.23%), followed by black (21.43%), white (10.20%) and others (7.14%). The African, Amerindian and European ancestry contribution estimated were 35.33%, 11.31% and 53.35% respectively (R2 = 0.998). Two mutations were detected the BRCA1 3450del4 in five patients (4.90%) and the BRCA1 c.211A>G in two patients (2.04%). All patients with these mutations were from State of Bahia and self-reported as mulatto or white. Any carrier declared as Spanish descendant. Conclusion: Although the Portuguese settled Brazil, here it was observed that this population seems to have high Spanish ancestry contribution, due to the high frequency of the BRCA1 3450del4 and c.211A>G (6.94%). It is also interestingly the absence of BRCA1 943ins10, because the State of Bahia has the higher rate of African-descendants in Brazil and most of the patients exhibited these physical traits (mulatto and black, 82.65%). Thus, high-risk patients from that region of Brazil could be screening first for the BRCA1 3450del4 and BRCA1 c.211A>G, where it has a founder effect. Citation Format: Ivana L Nascimento, Gabriela ES Felix, Camila A Sandes, Taisa B Machado-Lopes, Thais F Bomfim, Roberto Meyer, Maura Romeo, Betania Toralles, Kiyoko A Sandes. BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-13-02.