Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene Mutations on Overall Survival of Breast Cancer Based on TCGA Database.

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc.