title: Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients.
abstract: DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n=20) with acute side effects and the control group (n=20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P=0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P=0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P=0.037) vs control (r=-0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer.
authors.affiliation: Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. Electronic address: bahadirbatar@gmail.com.
authors.forename: Bahadir
authors.initials: B
authors.lastname: Batar
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Gulgun
authors.initials: G
authors.lastname: Guven
authors.affiliation: Department of Clinical Radiation Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Eroz
authors.affiliation: Department of Clinical Radiation Oncology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Nuran Senel
authors.initials: NS
authors.lastname: Bese
authors.affiliation: Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Guven
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: Acute side effects; DNA damage; DNA repair; XRCC1; breast cancer; radiation therapy