title: Association of XRCC5 VNTR polymorphism with the development of chronic myeloid leukemia.
abstract: Double-strand breaks (DSBs) inducing agents influence the fidelity of DNA repair in both normal cells and leukemic cells, causing major genomic instability. In eukaryotic cells, non-homologous end joining pathway (NHEJ) is the major mechanism for DSB repair. Human X-ray repair cross-complementing 5 (XRCC5) gene encodes for the protein KU86, an important component of NHEJ pathway. Variable number of tandem repeats (VNTR) polymorphism (rs 6147172) in the promoter region of XRCC5 gene was shown to have effect on gene expression and was found to be associated with the development of several cancers. We analyzed VNTR polymorphism of XRCC5 gene in 461 chronic myeloid leukemia (CML) cases and 408 controls by polymerase chain reaction. Our results showed that frequency of 0R/0R genotype was significantly elevated in CML cases compared to that of controls (p = 0.05). Significant difference in the genotype distribution was observed between cases and controls (p = 0.02). The risk of CML development was found to be elevated for individuals carrying lower repeats (1R p = 0.03; 0R p = 0.007). Elevated 0R/0R genotype frequency was found to be significantly associated with early age at onset (≤ 30 years) and slightly elevated in chronic phase and poor hematologic response to imatinib mesylate. The influence of zero repeat on enhanced expression of XRCC5 might confer risk to error-prone repair leading to genomic instability and CML. Hence, the VNTR polymorphism in the promoter region of XRCC5 gene could serve as an important prognostic marker in CML development.
authors: CSIR-SRF, Department of Genetics, Osmania University, Hyderabad, India, manjula.gorre@gmail.com.
authors: Manjula
authors: M
authors: Gorre
authors: Prajitha Edathara
authors: PE
authors: Mohandas
authors: Sailaja
authors: S
authors: Kagita
authors: Sandhya
authors: S
authors: Annamaneni
authors: Raghunadharao
authors: R
authors: Digumarti
authors: Vishnupriya
authors: V
authors: Satti
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D059766:DNA End-Joining Repair / Q000235:genetics*; D004265:DNA Helicases / Q000097:blood / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D000072200:Ku Autoantigen; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen
references: Mutat Res. 2008 Feb 1;638(1-2):26-36
references: 17904587
references: Cancer. 2001 Nov 1;92(9):2484-92
references: 11745306
references: World J Gastrointest Oncol. 2011 Dec 15;3(12):175-81
references: 22224172
references: Oncogene. 2001 Feb 8;20(6):739-47
references: 11314007
references: Cytogenet Cell Genet. 1994;65(4):221-7
references: 8258294
references: Gene. 1997 Oct 15;199(1-2):181-94
references: 9358055
references: Nucleic Acids Res. 1991 Oct 11;19(19):5444
references: 1681511
references: Cancer Res. 2003 Apr 15;63(8):1798-805
references: 12702565
references: Biochem Biophys Res Commun. 2012 Oct 26;427(3):503-5
references: 23022196
references: Biochem Biophys Res Commun. 2013 Jan 11;430(2):640-1
references: 23220236
references: Nat Genet. 2001 Mar;27(3):247-54
references: 11242102
references: Biochem Biophys Res Commun. 2012 Aug 24;425(2):398-400
references: 22842454
references: N Engl J Med. 1999 Jul 15;341(3):164-72
references: 10403855