BRCA1 and BRCA2 mutations in selected exons in breast cancer patients attending Mulago Hospital, Uganda

Abstract

Breast cancer 1 (BRCA1) and Breast cancer 2 (BRCA2), mutation recognition is crucial for cancer risk assessment, identification of suitable breast cancer treatments, and personalised breast cancer prophylaxis in mutation carriers. In Uganda, most patients are diagnosed between of 30 – 39 years, with high grade, triple negative (TN), and invasive ductal carcinomas. Although, these disease characteristic are suggestive of BRCA mutation occurrence among patients in Uganda, the frequency and nature of BRCA1 and Breast cancer 2 (BRCA2) mutations in patients in Uganda remains uncharacterised, thus affecting therapy. Exons 2 and 11 of BRCA1 and BRCA2 genes respectively harbour most mutations with increased breast cancer risk. On the other hand, exon 20 of BRCA1 is located at the 5’, a region associated with an increased risk to breast cancer. 83 breast cancer patients selected for the BRCA-mutation carrier enriching status and 157 age-matched non-related healthy individuals without known individual and / or family history of BRCA-associated cancers were enrolled into the study at Mulago hospital, Uganda. Exon 2 and 20 (BRCA1) together with the 16th fragment of exon 11 (BRCA2) were analysed for mutations using both polymerase chain reaction (PCR) and Sanger sequencing techniques. DNA multiple sequence alignment by MUSCLEWS with default parameters showed no mutations in exons 2 (58 cases and 100 controls) and 20 (82 cases and 151 controls) of the BRCA1 gene. Four mutations; T>A at Chr13:32914526, insC at Chr13:32914526-27, C>A at Chr13:32914528 and delG at Chr13:32914520, representing a frequency of 4.9% in the 82 breast cancers patients with invasive ductal carcinoma, grade 3, were identified in the 16th fragment of exon 11 of the BRCA2 gene irrespective of age. No BRCA2 mutations were identified in the male breast cancer cases as well as in the 106 controls studied for 16th fragment of exon 11. A study elucidating the significance of the detected BRCA2 mutations to breast cancer in Uganda should be carried out.