Analysis of brca1/2 mutations and performance of manchester scoring system in high risk iranian breast cancer patients: a pilot study

Haniye Jafardokht bonjar,1,* Iraj shahreki,2 Nazanin yousefian miandoab,3 Yalda khani,4 Safa shahmorad zade,5 Mahla sedighi nia,6

1. Nurse Student, Young Researcher Club member, Islamic Azad University, Zahedan, Iran
2. Instructor, Department of Children, School of Nursing and Midwifery, Islamic Azad University, Zahedan, Iran
3. Instructor of Medical Surgical Nursing School of Nursing and Midwifery Community Nursing Research Center Zahedan University of Medical Sciences, zahedan , Iran
4. Instructor, Department of surgery, School of Nursing and Midwifery, Islamic Azad University, Zahedan, Iran
5. Nurse, Zahedan University of Medical Sciences, zahedan , Iran
6. Nurse Student, Islamic Azad University, Zahedan, Iran

Abstract

Introduction

Pathogenic mutations in brca1 and brca2 genes account for 20-25% of familial breast cancer. brca1 and brca2 mutation frequencies differ considerably among various geographic regions and ethnicities. most studies have primarily used caucasian populations to delineate the population and family risks associated with germline brca1 and brca2 mutations, leaving patients of other ancestries understudied. as genetic testing for brca1 and brca2 mutations is underused in iran, it is of great importance to be able to describe the mutation spectrum of these genes and subsequently the genetic risks and testing benefits particular to iranian population.

Methods

We designed a pilot study to identify the full spectrum of brca1 and brca2 sequence variations and large single or multi-exonic deletions in 20 iranian breast cancer patients with a high likelihood of hereditary predisposition to breast cancer. manchester score, as a validated scoring system for probability of carrying a brca1/2 mutation, was calculated for all patients to determine the cut-off value for genetic testing in iranian families

Results

two pathogenic [c.4566c>g (p.tyr1522ter), c.1961dela (p.lys654serfs*47)] and one likely pathogenic (c.5153-26a>g) variants in brca1 and two pathogenic variants [c.8165c>g (p.thr2722arg), c.92g>a (p.trp31ter)] in brca2 gene were identified. assuming a manchester score of 20 points as cut-off value to perform brca genetic testing, this scoring system has a sensitivity of 80%, specificity of 60%, positive predictive value (ppv) of 40%, and negative predictive value (npv) of 90%.

Conclusion

considering high cost of testing in iran, it seems that that the cutoff value of 20 points is more appropriate.

Keywords

Analysis. iran. breast cancer