Low prevalence of BRCA1 and BRCA2 mutations in the sporadic breast cancer of Spanish population

Abstract

The true prevalence of BRCA1/BRCA2 (BRCAs) germline mutations in sporadic breast or ovarian cancer (SBC/SOC) in Caucasian population is not well established. The aim of the study is to establish the prevalence of BRCAs mutations in SBC to ponder its relevance in the programs of genetic counseling in cancer and to explore the genotype-phenotype relationship of these particular breast cancers. The study was performed in 495 SBC. We sought 46 BRCA1 and 53 BRCA2 pathogenic mutations reported in the Spanish population. We followed a high resolution melting method performed in the LightCycler 480 (Roche Diagnostics) for the screening of these Spanish mutations using 49 primer pairs. Eight different deleterious mutations, one of them novel, were detected in nine patients, five without family history of BC/OC, what yields a true prevalence of 1.05% for BRCAs mutations in SBC. Furthermore, we found 18 unknown variants. Larger tumour size (T > 1) and earlier presentation are the independent parameters associated with the presence of BRCAs pathogenic mutations in SBC (P < 0.01) and the BRCA1 mutations carriers develop steroid-receptors negative tumors. Our results indicate that the true prevalence of BRCAs germline deleterious mutations in SBC of Spaniards is low. However, this does not lessens its relevance since the presence of BRCAs mutations in SBC could represent circa 16% of total BRCAs mutations detected in BC. SBCs of BRCAs mutation carriers have phenotype more aggressiveness than SBC without BRCAs mutation.

Mutational analysis of BRCA1/2 gene and pathologic characteristics from Kazakh population with sporadic breast cancer in northwestern China

“…The average age of onset of BRCA1 and BRCA2 carriers in our study was similar to that in Chinese and Caucasian populations (Yip et al, 2009;Zhang et al, 2012), indicating that BRCA1/2 mutations may contribute to the early onset of breast cancer development in Kazakh women. Invasive ductal carcinoma is the most common histological subtype found among Kazakh breast cancer patients, but it was not the predominant histological tumor type in BRCA1/2 carriers in our cohort, which differed from the results observed in a Chinese Han population (de Juan Jiménez et al, 2012).…”

“…Despite differences in the method of collecting data, the study populations and the distributions of clinical-pathologic variables considered in our study were fundamentally consistently between the 2 hospitals. The prevalence of germline mutations in BRCA1/2 varied by ethnicity (De Leon Matsuda et al, 2002;Cherbal et al, 2012;de Juan Jiménez et al, 2012;Stadler et al, 2012;Kim and Choi, 2013;Tariq et al, 2013;Hernández et al, 2014). We observed a higher prevalence of BRCA1/2 common polymorphisms in breast cancer cases and the control group and also found that a large number of Kazakh women carried ≥ 4 co-existing BRCA1/2 alterations, which is consistent with the previously reported findings for Kazakhstan (Akilzhanova et al, 2011) and Asian and European populations (Han et al, 2006;Song et al, 2006;Loizidou et al, 2007).…”

“…A previous study suggested that BRCA1/2 germ line mutations occur in sporadic breast cancers (de Juan Jiménez et al, 2012), but whether common polymorphisms play an important role in cancer risk is not well-understood. In our study, we found 2 unclassified variants, rs80357374 (BRCA1 T539M) and rs4987117 (BRCA2 T1915M), one of which had not been found elsewhere in China (BRCA1 T539M) and was only detected in 2 healthy women.…”

Expression of BRCA1 and BRCA2 proteins and their correlation with clinical staging in breast cancer

“…[7,17] Our earlier studies for BRCA1 and BRCA2 mutations in breast cancer patients showed somatic missense mutation in BRCA1 gene patients, whereas no mutation was detected in BRCA2 gene. [18] In this report, considering the potential overlapping tumor suppressor role of BRCA1 and BRCA2 genes [19] and lack of any germline mutations in these genes during sporadic breast cancer, we analyzed an in situ expression of BRCA1 and BRCA2 proteins and investigated the correlation, if any, among the expression dynamics of the two proteins.…”

“…[6] Although somatic mutations have not been well characterized, loss of heterozygosity, decreased levels of BRCA1 mRNA and protein expression and methylation of the BRCA1 promoter region have been shown in some sporadic breast carcinoma, indicating the involvement of BRCA1 even in sporadic form. [7,8] Studies have indicated that the promoter region of BRCA1 gene has been found to be hypermethylated in most of the sporadic cases of breast cancer. This is indicative of interference with the expression of the gene leading to the abnormal expression of the protein.…”