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. 2019 Sep 11;17:27.
doi: 10.1186/s13053-019-0125-5. eCollection 2019.

Spectrum and Prevalence of BRCA1/2 Germline Mutations in Pakistani Breast Cancer Patients: Results From a Large Comprehensive Study

Free PMC article

Spectrum and Prevalence of BRCA1/2 Germline Mutations in Pakistani Breast Cancer Patients: Results From a Large Comprehensive Study

Muhammad Usman Rashid et al. Hered Cancer Clin Pract. .
Free PMC article


Background: Pathogenic germline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers worldwide. To refine the spectrum of BRCA1/2 mutations and to accurately estimate the prevalence of mutation in the Pakistani population, we studied 539 breast cancer patients selected for family history and age of diagnosis.

Methods: Comprehensive screening for BRCA1/2 germline mutations was performed using state-of-the-art technologies.

Results: A total of 133 deleterious mutations were identified in 539 families (24.7%), comprising 110 in BRCA1 and 23 in BRCA2. The prevalence of BRCA1/2 small-range mutations and large genomic rearrangements was 55.4% (36/65) for families with breast and ovarian cancer, 27.4% (67/244) for families with two or more cases of breast cancer, 18.5% (5/27) for families with male breast cancer, and 12.3% (25/203) for families with a single case of early-onset breast cancer. Nine mutations were specific to the Pakistani population. Eighteen mutations in BRCA1 and three in BRCA2 were recurrent and accounted for 68.2% (75/110) and 34.8% (8/23) of all identified mutations in BRCA1 and BRCA2, respectively. Most of these mutations were exclusive to a specific ethnic group and may result from founder effects.

Conclusions: Our findings show that BRCA1/2 mutations account for one in four cases of hereditary breast/ovarian cancer, one in five cases of male breast cancer, and one in eight cases of early-onset breast cancer in Pakistan. Our study suggests genetic testing of an extended panel of 21 recurrent BRCA1/2 mutations for appropriately selected patients and their families in Pakistan.

Keywords: BRCA1/2; Pakistan; breast cancer; germline mutations.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing of interests.


Fig. 1
Fig. 1
Flow diagram for the study participant’s enrollment, screening methods used and BRCA1/2 mutations detected
Fig. 2
Fig. 2
Distribution of deleterious germline mutations identified in Pakistani breast/ovarian cancer families across the BRCA1 and BRCA2 genes. Recurrent mutations are marked with (RM). The distribution of breast cancer (BC) and ovarian cancer (OC) in families according to the position of the mutations in BRCA1 (a) and BRCA2 (b) is shown. Regions inferred to be breast cancer cluster regions (BCCRs) and ovarian cancer cluster regions (OCCRs) according to Rebbeck and colleagues [24] are shown at the bottom

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