Zeinab Hallajian1, Frouzandeh Mahjoubi2, Nahid Nafissi1. 1. Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. 2. Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. frouz@nigeb.ac.ir.
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 (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.
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.
Entities:
Keywords:
ATM; BRCA1; Breast cancer; RAD51; Real Time PCR
Authors: Fábio Santiago; Rafaele Tavares Silvestre; Ubirani Barros Otero; Marianne Medeiros Tabalipa; Marilza de Moura Ribeiro-Carvalho; Luciano Rios Scherrer; Ahmed Al-Rikabi; Thomas Liehr; Gilda Alves; Maria Helena Ornellas Journal: Int Arch Occup Environ Health Date: 2021-03-28 Impact factor: 3.015