Hereditary breast and ovarian cancer in Andalusian families: a genetic population study

Abstract

BackgroundThe BRCA1/2 mutation profile varies in Spain according to the geographical area studied. The mutational profile of BRCA1/2 in families at risk for hereditary breast and ovarian cancer has not so far been reported in Andalusia (southern Spain).MethodsWe analysed BRCA1/2 germline mutations in 562 high-risk cases with breast and/or ovarian cancer from Andalusian families from 2010 to 2015.ResultsAmong the 562 cases, 120 (21.4%) carried a germline pathogenic mutation in BRCA1/2; 50 in BRCA1 (41.7%) and 70 in BRCA2 (58.3%). We detected 67 distinct mutations (29 in BRCA1 and 38 in BRCA2), of which 3 in BRCA1 (c.845C > A, c.1222_1223delAC, c.2527delA) and 5 in BRCA2 (c.293 T > G, c.5558_5559delGT, c.6034delT, c.6650_6654delAAGAT, c.6652delG) had not been previously described. The most frequent mutations in BRCA1 were c.5078_5080delCTG (10%) and c.5123C > A (10%), and in BRCA2 they were c.9018C > A (14%) and c.5720_5723delCTCT (8%). We identified 5 variants of unknown significance (VUS), all in BRCA2 (c.5836 T > C, c.6323G > T, c.9501 + 3A > T, c.8022_8030delGATAATGGA, c.10186A > C). We detected 76 polymorphisms (31 in BRCA1, 45 in BRCA2) not associated with breast cancer risk.ConclusionsThis is the first study reporting the mutational profile of BRCA1/2 in Andalusia. We identified 21.4% of patients harbouring BRCA1/2 mutations, 58.3% of them in BRCA2. We also characterized the clinical data, mutational profile, VUS and haplotype profile.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4537-9) contains supplementary material, which is available to authorized users.

Genetic and clinical characterization of BRCA-associated Hereditary Breast and Ovarian Cancer in Navarra (Spain)

“…Mutations in BRCA1 and BRCA2 genes were identified in 16% of families (26% of individuals) included in the high-risk HBOC sample. This rate is comparable with other studies [21][22][23] and similarly shows a decreasing trend over time, moving from 30% in 2000-2005, to 17% during (2006-2010) and 14% from 2011 to 2016. This is, most likely, due to the referral of the most severely affected families in the first years of cancer genetic services, and the use of less strict inclusion criteria in the later period, given the decrease in cost of the molecular analysis.…”

“…Navarra is a small community in the North of Spain that has experienced important demographic changes since the 1950 decade, due to migration from other Spanish communities or countries. This mixed population could explain, at least in part, the similarities in BRCA1/2 mutation distribution and spectrum with other areas of Spain [23,24]. As previously reported national wide, with the exception of Galicia and Asturias [21,25], deleterious mutations in BRCA2 were more frequent than in BRCA1, particularly among families of local ancestors in which 2/3 of BRCA associated families carried a BRCA2 deleterious variant.…”

Analysis of Heterozygous BRCA1 5382ins Founder Mutation in a Cohort of Egyptian Breast Cancer Female Patients Using Pyrosequencing Technique

“…In the present study 3 out of 4 (75%) of the carrier group had 3 family members affected with cancers, Table 5. In line with our study, Pajares et al, (2018) reported that among the studied BRCA1-mutated families, the most frequent criterion was the presence of three or more family members with breast and/or ovarian cancer.…”

Genetic and clinical characterization of BRCA-associated hereditary breast and ovarian cancer in Navarra (Spain)

“…Previous studies have analysed the mutation spectrum of BRCA1/2 in different regions of Spain [13–19]. Navarra, with about 650,000 people in 2018, has historically been in exchange with the neighbouring Basque territories in the north and Aragon and Castile in the southeast; additionally, in the last decades, it has experienced migration from other Spanish communities and countries.…”