title: Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.
abstract: BACKGROUND
  DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes.
  
  
  METHODS
  50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009.
  
  
  RESULTS
  mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (Pvalue< 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (Pvalue< 0.0001). There was a significant association between down expression of ATM with stage (Pvalue< 0.05), necrosis (Pvalue< 0.05), perineural invasion (Pvalue< 0.05), vascular invasion (Pvalue< 0.01), malignancy (Pvalue≤ 0.001), PR (Pvalue< 0.05) and ER status (Pvalue< 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (Pvalue≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (Pvalue< 0.01), auxiliary lymph node metastasis (Pvalue= 0.01), age (P = 0.001), grade (Pvalue< 0.05) and PR status (Pvalue< 0.05).
  
  
  CONCLUSIONS
  This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.
authors.affiliation: Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Hallajian
authors.affiliation: Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. frouz@nigeb.ac.ir.
authors.forename: Frouzandeh
authors.initials: F
authors.lastname: Mahjoubi
authors.affiliation: Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Nafissi
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000556:secondary*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000556:secondary*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics*; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: ATM; BRCA1; Breast cancer; RAD51; Real Time PCR