Association of BRCA1 185 del AG with early age onset of breast cancer patients in selected cohort from Pakistani population

Background & Objective: Large spectrum of pathogenic BRCA mutations is known as a major cause of hereditary breast ovarian cancer in human all over the world. The objective of present study was to find out the association of mutations185-del-AG and 185Ins.A at BRCA1 exon-2 with age of onset and family history of gynecological cancer among the selected cohort of breast cancer patients in Pakistani population and to provide guidelines for treatment strategies.

Methods: For the present study 115 subjects were recruited from different hospitals of Punjab, Pakistan, during May, 2017 to February, 2018. The inclusion criteria were age ≥30, without any previous BRCA testing and willingness to participate in present study. Subjects were interviewed for various demographic factors. Out of 115 subjects, 46 were selected on the basis of findings of previous studies and approximately 3 ml of blood was collected in EDTA coated vials for analysis of BRCA1 exon-2. Column based DNA extraction was performed by using commercial kit and exon specific primers were used to amplify BRCA1 exon 2 and PCR products were sent for sequencing to Eurofins Genomics. Sequences were analyzed through the BLAST program at National Center for Biotechnology Information (NCBI) and Bio Edit software. Accession numbers were obtained on submission of sequences in GenBank.

Results: BRCA1-185-del AG mutation was found in one of the breast cancer patient who was 33 years of age at diagnosis. None of the samples revealed positive results for BRCA1-185 Ins. A.

Conclusion: BRCA1-185 Del AG mutation has association with early age onset of breast cancer. The direct sequencing is very useful approach for BRCA analysis and exon specific selected cohort from Pakistani population.