BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history

Abstract

Certain genetic predisposition factors, such as BRCA1 and BRCA2 mutations play a pivotal role in familial breast cancer development in both males and females. Due to this, the importance and necessity of genetic screening to identify mutations affecting the population is paramount. Undergoing genetic screenings allows for a more knowledgeable risk assessment for the patients and their care providers. The aim of this study was to evaluate the prevalence of BRCA1/BRCA2 mutated genes in the Turkish population among unselected patients. To identify the molecular markers, we utilized a gene panel analysis consisting of BRCA1 and BRCA2 genes, with a next generation sequencing platform (MiSeq System, Illumina). Sequencing was performed using leukocyte DNA from breast cancer patients. In‐silico analysis for novel mutations was carried out using SIFT, PolyPhen2 and MutationTaster. BRCA1 and BRCA2 pathogenic variants were identified in 18 of 129 (14%) patients among the study population; of those 18 patients, seven (39%) were found in the BRCA1 gene and 11 (61%) in the BRCA2 gene. Ten of the eleven BRCA2 variants (90%) were novel mutations. Four of ten (40%) of the novel mutations were determined to be deleterious and six out of ten (60%) were identified as single nucleotide variations. Clinically significant mutations of the BRCA1/BRCA2 genes are related to an increased susceptibility for breast cancer. There is however, little known about BRCA mutations amongst the general population. Thus, it is important that patients are able to undergo genetic screenings and counseling. This also allows for greater care from health care providers and can only facilitate disease prevention which in turn can lead to a decreased cancer morbidity rate.

Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey

“…We think that other cancer related genes may play an important role for cancer predisposition and progression, and should be considered for further investigation. Additionally, the positivity rates were similar with our previous study of 129 patients with a different cohort of breast cancer cases due to the only shared data focusing on selected Turkish cases independent of family history [ 16 ].…”

“…In contrast with the literature and our previous study, we found more clinically- relevant variations in the BRCA2 gene than BRCA1 . The majority of these BRCA2 variants were classified as VUS and likely pathogenic rather than pathogenic [ 16 ]. We assume the reason is due to the lack of an in depth research on many of these Turkish-population-specific BRCA variants.…”

Comparison of Clinicopathological Characteristics of BRCA1 and BRCA2 Carriers with Breast Cancer: The Role of Ki-67 Index

“…There are limited studies investigating BRCA mutations in Turkey, and the BRCA carriage rates in patients with breast cancer are not known. [16][17][18] BRCA1 carriage was observed more frequently in some studies, while BRCA2 carriage in others, as in our study. On the other hand, the presented BRCA1 and BRCA2 frequencies fail to reflect the general population rates, since the study we presented was not conducted to elucidate the BRCA carrier frequency of the population.…”

Oral Contraceptive Use and Breast Cancer Risk According to Molecular Subtypes Status: A Systematic Review and Meta-Analysis of Case-Control Studies

“…BrCa death rates were significantly higher in developed countries compared to developing countries (15.0 vs. 12.8 per 100,000) [1,2]. Most cases of BrCa are sporadic, but an estimated 5-10% have a genetic predisposition related to, among other things, a family history of cancer in first-degree relatives or carrying genetic mutations [3,4].…”