Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

Abstract

Background Breast cancer is the most common malignancy in women worldwide. About 5%–10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next‐generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes. Methods Twenty‐five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon–intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS. Results We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer. Conclusion Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives.

Genetic Predisposition of Breast Cancer in the United Arab Emirates

“…Multiple genes were detected in Qatar during 2013 to 2018 that are associated with breast cancer, similar to many studies BRCA1 was the most common mutation detected, followed by BRCA2 [8]. Similarly, BRCA1 mutations were mostly associated with hereditary breast cancer in Oman and Bahrain [9,10].…”

Actionable genomic variants in 6045 participants from the Qatar Genome Program

“…We also found four QGP subjects carry the mutation c.4850C>A (p.Ser1617*) in BRCA1 . This variant is known to be associated with familial breast/ovarian cancer and with the hereditary cancer‐predisposing syndrome (Al Hannan et al, 2019). Out of four QGP subjects, three have a family history of cancer (mother with breast cancer, a mother with endometrium cancer, and a father with bowel cancer).…”

Identification of Some Breast Cancer Related Genes by RAPD Technique in Maysan Province, Iraq

“…The total polymorphic bands in the BC patient of AB-CG2,ER-α ,mi-RNA 152 genes were (15,18,8 ) respectively, while in control were (14,34,0) bands; The total monomorphic bands in ABCG2,ER-α ,mi-RNA 152 genes of the patients were (12,16,8 ) respectively; while in control were (16, 0, 12) bands; The total unique bands in ABCG2, ER-α, mi-RNA 152 genes were (10, 5, 2) bands in a patient; while in control were (6, 7, 0) bands, as shown in figure (3) and table (3,4,5,6,7,8,9,10,11).…”

“…In Iraq, it is the most typical type of female malignancy, accounting for approximately one-third of the registered female cancers according to the Iraqi cancer registry in 2004 2,3 . About 5-10% of breast cancer is inherited 4 ; while 90-95% is sporadic and revealed randomly and is not predetermined genetically 5,6 .…”