Breast Cancer High-Penetrance Genes BRCA1 and BRCA2 Mutations Using Next-Generation Sequencing Among Iraqi Kurdish Women.

Background and genes are the main high-penetrance genes that are responsible for most cases of inherited breast cancer. The present study aimed to detect the frequencies of inherited breast cancer caused by and genes among Kurdish breast cancer patients, including all the exome of these two genes, using next-generation sequencing (NGS). Methodology Seventy women who were diagnosed with breast cancer and registered at Nanakali Hospital in Erbil, Iraq, were included. Blood samples were collected for molecular testing (polymerase chain reaction (PCR)) targeting all exomes of and genes. All exome regions are sequenced by NGS using the Miseq system (Illumina Inc., San Diego, CA). Obtained data were visualized using Integrative Genomics Viewer (IGV 2.3 Software, Broad Institute, Cambridge, MA). Data were interpreted based on the National Center for Biotechnology Information (NCBI), Clinically Relevant Variation (ClinVar) archives, and other databases. Results Among 70 samples, more than forty-two variants have been detected, 20 on and 22 on . Regarding clinical significance, six (14.28%) variants were pathogenic, four of them on the  gene, which were: c.3607C>T, c.3544C>T, c.68_69del, and c.224_227delAAAG, and two pathogenic variants were on gene: c.100G>T, and c.1813delA. Also, two (4.76%) variants were conflict interpretations of pathogenicity, one (2.38%) was a variant of uncertain significant VUS, and the rest 29 (69%) variants were benign. In addition, four new variants (three in and one in gene), never previously reported, were identified. Conclusions In conclusion, analyzing the genes provide a better prediction for the risk of developing breast cancer in the future. Variant types and frequencies differ among different populations and ethnicities, the common mutations worldwide may not be prevalent in the Kurdish population. The current research findings will be useful for future screening studies of these two genes in the Kurdish population.