Screening for Del 185 AG and 4627C>A BRCA1 Mutations in Breast Cancer Patients from Lahore, Pakistan

  • Aziz, Faiza (Department of Microbiology and Molecular Genetics, University of the Punjab) ;
  • Fatima, Warda (Department of Microbiology and Molecular Genetics, University of the Punjab) ;
  • Mahmood, Saqib (Department of Allied Health sciences, University of Health Sciences) ;
  • Khokher, Samina (Surgical Specialist Unit, Services Hospital)
  • Published : 2016.06.01


Breast cancer contributes to approximately 23% of the cancer cases identified and 14% of cancer related deaths worldwide. Including a strong association between genetic and environmental factors, breast cancer is a complex and multi factorial disorder. Two high penetration breast cancer susceptibility genes (BRCA1 and BRCA2) have been identified, and germ line mutations in these are thought to account for between 5% and 10% of all breast cancer cases. The human BRCA1 gene, located on 17q, is involved in the regulation of cell proliferation by aiding in DNA repair, transcriptional responses to DNA damage and cell cycle check points. Mutations in this gene enhance cell proliferation and facilitate formation of tumors. Two mutations, the 185 deletion of AG and the 4627 substitution from C to A, are founder mutations in the BRCA1 gene for breast cancer in Asian populations. Allele specific PCR was performed to detect these selected mutations in 120 samples. No mutation of 4627 C to A was detected in the samples and only one of the patients had the 185 del AG mutation in the heterozygous condition. Our collected samples had lower consanguinity and family history indicating the greater involvement of environmental as compared to genetic factors.


  1. Adami HO, Malker B, Holmberg L, et al (1986). The relation between survival and age at diagnosis in breast cancer. New Engl J Med, 315, 559-63.
  2. Asif HM, Sultana S, Akhtar N, et al (2014). Prevalence, risk factors and disease knowledge of breast cancer in Pakistan. Asian Pac J Cancer Prev, 15, 4411-6.
  3. Assi HA, Khoury KE, Dbouk H, et al (2013). Epidemiology and prognosis of breast cancer in young women. J Thorac Dis, 5, 2.
  4. Ayub M, Firdous K, Rizwan H, et al (2015). Awareness status of breast cancer in Pakistan society among affected women with breast cancer and control men and women: a cross-sectional study. J Chem Bio Phy Sci Sec B, 5, 3860-70.
  5. Aziz Z, Sana S, Saeed S, et al (2003). Institution based tumor registry from Punjab: five year data based analysis. J Pak Med Assoc, 53, 350-53.
  6. Ban KA, Godellas CV (2014). Epidemiology of breast cancer. Surg Oncol Clin N Am, 23, 409-22.
  7. DeSantis C, Ma J, Bryan L, et al (2014). Breast cancer statistics, 2013. CA-Cancer J Clin, 64, 52-62.
  8. Friedenson B (2007). The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers. BMC Cancer, 7, 152.
  9. Hanif M, Zaidi P, Kamal S, et al (2009). Institution-based cancer incidence in a local population in Pakistan: nine year data analysis. Asian Pac J Cancer Prev, 10, 227-30.
  10. Hansa J, Kannan R, Ghosh SK (2012). Screening of 185DelAG, 1014DelGT and 3889DelAG BRCA1 mutations in breast cancer patients from North-East India. Asian Pac J Cancer Prev, 13, 5871-4.
  11. Liede A, Malik IA, Aziz Z, et al (2002). Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan. Am J Hum Genet, 71, 595-606
  12. Malik IA (2002). Clinico-pathological features of breast cancer in Pakistan. J Pak Med Assoc, 52, 100-3
  13. Petrisek A, Campbell S, Laliberte L (2000). Family history of breast cancer. Cancer Pract, 8, 135-42.
  14. Rashid MU, Zaidi A, Torres D, et al (2006). Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. Int J Cancer, 119, 2832-9.
  15. Walsh T, Lee MK, Casadei S, et al (2010). Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci, 107, 12629-33.