title: Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals.
abstract: BACKGROUND
  A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it.
  
  
  METHODS
  By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity.
  
  
  RESULTS
  The rs2267437 polymorphisms in XRCC6 was associated (P=0.0326) with increased DSB induction while rs1805388 in LIG4 (P=0.0240) was associated with increased radioresistance. Further, multiple risk alleles decreased the DSB repair capacity in an additive manner. Polymorphisms in candidate DSB repair genes can act individually or in combination to the efficacy of DSB repair process, resulting in variation of cellular radiosensitivity.
  
  
  CONCLUSIONS
  Current study suggests that γ-H2AX assay may fulfil the role of a rapid and sensitive biomarker that can be used for epidemiological studies to measure variations in radiosensitivity. DSB repair gene polymorphisms can impact the formation and repair of DSBs.
  
  
  CONCLUSIONS
  γ-H2AX foci analysis as well as DSBs repair gene polymorphisms can be used to assess cellular radiosensitivity, which will be useful in population risk assessment, disease prediction, individualization of radiotherapy and also in setting the radiation protection standards.
authors.affiliation: Department of Radiation Biology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Kamalesh Dattaram
authors.initials: KD
authors.lastname: Mumbrekar
authors.affiliation: Department of Radiation Biology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Hassan Venkatesh
authors.initials: HV
authors.lastname: Goutham
authors.affiliation: Department of Radiation Oncology, Manipal Hospital, Bangalore, Karnataka, India.
authors.forename: Bejadi Manjunath
authors.initials: BM
authors.lastname: Vadhiraja
authors.affiliation: Department of Radiation Biology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India. Electronic address: satishraomlsc@gmail.com.
authors.forename: Satish Rao
authors.initials: SR
authors.lastname: Bola Sadashiva
mesh_terms: D000328:Adult; D000368:Aged; D053903:DNA Breaks, Double-Stranded; D000072481:DNA Ligase ATP / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*; D059767:Recombinational DNA Repair; D014965:X-Rays
chemical_list: C000607893:LIG4 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP
keywords: DNA repair; Double strand break; Radiosensitivity; SNP; γ-H2AX