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.
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.
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).
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.
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This research was financially supported by the National Institute of Genetic Engineering and Biotechnology Grant No: 412 M, Tehran, Iran.
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The authors declare that they have no conflict of interest.
Human rights statement and informed consent
All procedures followed were approved by the local ethical standards of National Institute of Genetic Engineering and Biotechnology (NIGEB) with IR.NIGEB.EC.1395.5.6.B approval number. Written informed consent was obtained from each patient who participated in this study prior to sample collection.
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Hallajian, Z., Mahjoubi, F. & Nafissi, N. Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients. Breast Cancer 24, 624–634 (2017). https://doi.org/10.1007/s12282-016-0750-z