title: Ataxia telangiectasia-mutated gene polymorphisms and acute normal tissue injuries in cancer patients after radiation therapy: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Studies of the association between ataxia telangiectasia-mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings.
  
  
  METHODS
  Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted.
  
  
  RESULTS
  The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries.
  
  
  CONCLUSIONS
  Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury. These support the evidence of an association between the rs1801516 polymorphism and acute radiation injuries, encouraging further research of this topic.
authors.affiliation: Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Internal Medicine, Nanling School District Hospital of Jilin University; Changchun, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Tang
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cong
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, China. Electronic address: fujun_han@aliyun.com.
authors.forename: Fujun
authors.initials: F
authors.lastname: Han
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D015994:Incidence; D009369:Neoplasms / Q000532:radiotherapy*; D011110:Polymorphism, Genetic; D011832:Radiation Injuries / Q000453:epidemiology / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D005819:Genetic Markers; D064007:Ataxia Telangiectasia Mutated Proteins