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The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients

  • Mohamed Saleem
  • Mohd Bazli Ghazali
  • Md Azlan Mohamed Abdul Wahab
  • Narazah Mohd Yusoff
  • Hakimah Mahsin
  • Ch’ng Ewe Seng
  • Imran Abdul Khalid
  • Mohd Nor Gohar Rahman
  • Badrul Hisham YahayaEmail author
Part of the Advances in Experimental Medicine and Biology book series


Approximately 5–10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3′-subhaplotype CGC displayed strong LD with 5′-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.


BRCA1 BRCA2 Breast cancer Early onset 



Authors would like to extend nurses and technical staff in the Department of Surgery, Hospital Seberang Jaya, Ministry of Health Malaysia, Hospital Universiti Sains Malaysia (HUSM) and Clinical Trial Centre, and Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia for helping us in sample collection and patient recruitments.

Conflict of Interests



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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Mohamed Saleem
    • 1
    • 2
  • Mohd Bazli Ghazali
    • 1
    • 5
  • Md Azlan Mohamed Abdul Wahab
    • 1
  • Narazah Mohd Yusoff
    • 1
  • Hakimah Mahsin
    • 3
  • Ch’ng Ewe Seng
    • 4
  • Imran Abdul Khalid
    • 5
  • Mohd Nor Gohar Rahman
    • 6
  • Badrul Hisham Yahaya
    • 1
    Email author
  1. 1.Regenerative Medicine Cluster, Advanced Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia
  2. 2.Genomix Lab Sdn BhdPetaling JayaMalaysia
  3. 3.Pathology DepartmentSeberang Jaya HospitalSeberang PraiMalaysia
  4. 4.Oncology and Radiological Sciences Cluster, Advanced Medical and Dental InstituteUniversiti Sains MalaysiaPenangMalaysia
  5. 5.Surgery DepartmentSeberang Jaya HospitalSeberang PraiMalaysia
  6. 6.Surgery Department, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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