Screening BRCA1 and BRCA2 mutation frequencies in breast cancer patients of west Iran reveals a novel polymorphism in BRCA1 gene

Abstract

Introduction: Breast Carcinoma is the most prevalent cancer in women worldwide. Mutations and polymorphisms of BRCA1 and BRCA2 gens are among the most important predisposing variants BC. The existing variants in these genes are highly heterogeneous, therefore study of these variants in a population could yield different findings from another. As a result, study of such genes seems necessary to determine and screen for the most important mutations in each region to assist in counseling of predisposed individuals. 

Mterial and methods: This case-control study was conducted on 140 women with breast carcinoma and 140 healthy individuals. After the consent was obtained, 5cc peripheral blood was taken from each individual for molecular tests. Then, the genomic DNA was extracted and Multiplex PCR was run for 185del AG and 5382insC in BRCA1 and 6174 delT in BRCA2. The results of Multiplex PCR were observed on polyacrylamide gel. Then, the samples with shifted bands on the gel were proved with direct DNA sequencing.

Findings: In the studied samples, none of the above mutations were observed by sequencing, but C>G was detected at position 5265 in the coding region of the BRCA1 gene. In view of the investigations, this variation is a new polymorphism in BRCA1.

Conclusion: The variant detected in BRCA1 gene causes variation in the third codon of amino acid serine and develops another codon for the same amino acid. Therefore, the detected variant is classified as silent and does not exist in the conserved region. The variant has not yet been reported. As a result, the effect of such variation on increased predisposition to BC or its association with the disease needs study of more samples.