Haplotype Analysis of BRCA1 Gene D17S855 and D17S1322 Markers in Iranian Familial Breast Cancer Patients

  • Published : 2016.07.01


Background: Breast cancer molecular analysis by linkage analysis has the advantage of facilitating early diagnosis in asymptomatic genetic carriers, with a view to the preventive follow-up of these subjects and genetic counseling. The aim of this study was to evaluate BRCA1 gene D17S855 and D17S1322 markers in breast cancer patients. Materials and Methods: A series of 85 BC patients and 85 unrelated healthy women were recruited for haplotype analysis performed using two short tandem repeat markers located within the BRCA1 gene locus. Each marker was amplified with PCR genomic DNA from each individual and fluorescently end-labeled primers. Results: Both D17S855 and D17S1322 markers included 12 kinds of alleles. Results indicate that most of the BC patients shared two common 121-150 (11.2%, RR=1.56 and p=0.02) and 121-146 (5.6%, RR=1.9 and p=0.02) haplotypes. Conclusions: Our results should be helpful to understand the haplotype phase in the BRCA1 gene and establish a genetic screening strategy in the Iranian population.


  1. Alsop K, Fereday S, Meldrum C, et al (2012). BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian ovarian cancer study group. J Clin Oncol, 30, 2654-63.
  2. Clark SL, Rodriguez AM, Snyder RR, (2012). Structure-Function Of The Tumor Suppressor BRCA1. Comput Struct Biotechnol J. Research Network Computational Structural Biotechnol, 1, 1-8.
  3. De La Hoya M, Sulleiro S, Osorio A, et al (2002). Clustering of cancer-related mutations in a subset of BRCA1 alleles: A study in the Spanish population. Int J Cancer, 100, 618-9.
  4. Haiman CA, Stram DO, Pike MC, et al (2003). A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort. Hum Mol Genet, 12, 2679-92.
  5. Forat-Yazdi M, Neamatzadeh H, Sheikhha MH, et al (2015). BRCA1 and BRCA2 common mutations in Iranian breast cancer patients: a meta-analysis. Asian Pac J Cancer Prev, 16, 1219-24.
  6. Friedenson B (2005). BRCA1 and BRCA2 Pathways and the risk of cancers other than breast or ovarian. Med Gen Med, 7, 60.
  7. Laitman Y, Feng B-J, Zamir IM, et al (2012) Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations. Eur J Hum Genet. Nature Publishing Group, 21, 212-6.
  8. Mefford HC, Baumbach L, Panguluri RC, et al (1999) Evidence for a BRCA1 founder mutation in families of West African ancestry. Am J Hum Genet, 65, 575-8.
  9. Miresmaeili M, Kordi D M, Kalantar M, Moshtaghioun M (2016) Haplotype analysis of BRCA1 intragenic markers in Iranian patients with familial breast and ovarian cancer. Int J Reprod BioMed, 14, 271-4
  10. Neamatzadeh H, Shiryazdi SM, Kalantar SM (2015). BRCA1 and BRCA2 mutations in Iranian breast cancer patients: A systematic review. J Res Med Sci, 20, 284-93.
  11. Nowacka-Zawisza M, Brys M, Romanowicz-Makowska H, et al (2008). Dinucleotide repeat polymorphisms of RAD51, BRCA1, BRCA2 gene regions in breast cancer: Original Article. Pathol Int, 58, 275-81.
  12. Osorio A, de la Hoya M, Rodriguez-Lopez R, et al (2003). Over-representation of two specific haplotypes among chromosomes harbouring BRCA1 mutations. Eur J Hum Genet, 11, 489-92.
  13. Ticha I, Kleibl Z, Stribrna J, et al (2012). Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Czech high-risk breast/ovarian cancer patients: high proportion of population specific alterations in BRCA1 gene. Breast Cancer Res Treat, 124, 337-47.
  14. Walsh T, Casadei S, Coats KH, et al (2006). Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA, 295, 1379-88.