Abstract P2-09-12: Prevalence of Hispanic BRCA1 and BRCA2 mutations among HBOC patients from Southern Brazil reveal differences among Latin American populations
Authors: Alemar B , Herzog J , Ashton-Prolla P , Weitzel J 
Published: May 2016

Abstract
Background.Breast cancer (BC) is the most common malignancy in women around the world, and 5% of BC cases and 15% of ovarian cancer (OC) cases can be attributed to BRCA1 and BRCA2 germline mutations, configuring Hereditary Breast and Ovarian Cancer Syndorme (HBOC). Considering that the genetic similarities between Latin American populations are largely unknown, we aimed to address if a panel of Hispanic BRCA mutations could be useful for a Brazilian population. Methods.Unrelated patients fulfilling NCCN criteria for HBOC syndrome were recruited. ASCO, Myriad and Penn II clinical testing criteria were analyzed for all patients. Blood-derived DNA samples were screened for 114 BRCA mutations, in a panel estimated to account for up to 90% of all BRCA Hispanic mutations (HISPANEL), using the Sequenom MassArray platform. Results. Among a total of 233 unrelated patients included (225 women and 8 men), 85% were BC patients and 14 patients were cancer unaffected. The mean age at diagnosis was 43 years for BC affected individuals and 45 years for patients with OC. Fifty-three patients fulfilled ASCO criteria, and 182 had Penn II≥10%, while only 64 had a Myriad score ≥10%. BRCA mutations were detected in 9 of 233 patients (prevalence of 3.86%). Among BC and/or OC affected individuals, this prevalence was 4.22%. Features of mutation carriers are depicted in table 1.
Table 1. BRCA mutations identified in Brazilian HBOC patients Mutation Gender Tumor type and age at diagnosis Family history of cancer BRCA1 c.3331_3334delCAAGFemaleOvCa, 47; BrCa, 50Daughter BrCa≤20;Brother PrCa 54;Cousin BrCa≥ 50 BRCA1 c.5266dupCFemaleBilateral BrCa, 35 and 45Mother OvCa 58;Aunt OvCa 49;Cousin BrCa 49;Great-grandmother BrCa 90 BRCA1 c.5266dupCFemaleBrCa, 36Aunt BrCa 62;Cousin BrCa 45;Cousin BrCa 44;Cousin Bilateral BrCa 45;Cousin BrCa 44;Cousin OvCa 52 BRCA1 c.5266dupCFemaleOvCa, 52Mother OvCa 77;Sister BrCa 44;Aunt OvCa 66 BRCA1 c.5266dupCFemaleBilateral BrCa, 23 and 44Mother BrCa 45;Aunt Bilateral BrCa 48;Cousin BrCa 30;Aunt Bilateral BrCa 58;Grandmother BrCa BRCA1 c.5266dupCFemaleBilateral BrCa, 26Sister BrCa 50;Niece BrCa 28;Niece BrCa 30 BRCA1 c.5266dupCMaleBrCa, 64Daughter BrCa 34;Sister BrCa≤ 50;Sister BrCa 32 BRCA2 c.2806_2809delAAACFemaleBrCa, 49Sister BrCa 32;Sister BrCa 44;Aunt Bilateral BrCa 40 and 55 BRCA2 c.2806_2809delAAACFemaleBilateral triple negative BrCa, 42 and 55NoneBrCa=breast cancer; OvCa=ovarian cancer.
Conclusions. The HISPANEL detects 59 BRCA1 and 55 BRCA2 mutations, including some mutations previously reported in Brazilian individuals. Most mutation carriers had the BRCA1 c.5266dupC (5382insC) mutation, a common founder mutation in several populations. Our results are largely different from other Latin American published data. Although low BRCA prevalence mutational rates were also seen in Peru and Mendellín (Colombia), in Mexico and Bogota (Colombia) a prevalence of 27% and 15%, respectively, was found in studies using HISPANEL and all studies included patients unselected for family history. Our findings reinforce that different Latin-American populations have different BRCA mutational profiles.
Citation Format: Alemar B, Herzog J, Ashton-Prolla P, Weitzel J. Prevalence of Hispanic BRCA1 and BRCA2 mutations among HBOC patients from Southern Brazil reveal differences among Latin American populations. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-12.