Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.
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 (P value < 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (P value < 0.0001). There was a significant association between down expression of ATM with stage (P value < 0.05), necrosis (P value < 0.05), perineural invasion (P value < 0.05), vascular invasion (P value < 0.01), malignancy (P value ≤ 0.001), PR (P value < 0.05) and ER status (P value < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P value ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P value < 0.01), auxiliary lymph node metastasis (P value = 0.01), age (P = 0.001), grade (P value < 0.05) and PR status (P value < 0.05).


CONCLUSION
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.
['Hallajian|Zeinab|Z|', 'Mahjoubi|Frouzandeh|F|', 'Nafissi|Nahid|N|']
D064007:Ataxia Telangiectasia Mutated Proteins D019313:BRCA1 Protein D014408:Biomarkers, Tumor D001943:Breast Neoplasms D018270:Carcinoma, Ductal, Breast D018275:Carcinoma, Lobular 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 D015996:Survival Rate
ATM BRCA1 RAD51 Breast cancer Real Time PCR