title: A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.
abstract: OBJECTIVE
  To examine the association of tag single nucleotide polymorphisms (tagSNPs) (rs1130409, rs1760944, rs2307486 and rs3136817) in APEX1 with the risk of severe radiation-induced pneumonitis (RP) after radiotherapy among Han Chinese patients with lung cancer.
  
  
  METHODS
  A total of 168 patients with lung cancer who were receiving radiotherapy were prospectively recruited. RP was evaluated according to the Radiation Therapy Oncology Group. A case-control study was performed. The case group included patients with RP grade of ≥3, while the control group comprised patients with RP grades <3. Four tagSNPs of APEX1 were genotyped in 126 patients with complete follow-up by multi-SNaPshot® (Genesky Biotechnologies Inc., Shanghai, China) genotyping assays. RESULTS were assessed by a logistic regression model for RP risk and Mantal-Cox log-rank test for the cumulative RP probability by the genotypes.
  
  
  RESULTS
  rs1130409 was associated with severe RP. GT genotype of rs1130409 was significantly higher in patients with RP than in those of the control group [68.8% vs 41.8%; p = 0.025; resulting odds ratio (OR), 5.98]. Patients with lung cancer bearing the G allele had a 5.83-fold higher risk of RP than those with the wild TT genotype [OR = 5.83; 95% confidence interval (CI), 1.27-26.90; p = 0.024], and this was further confirmed by the binary regression adjusted by some confounding factors, including Karnofsky performance scale, concurrent chemotherapy-radiotherapy and lung volume receiving >30 Gy (OR = 6.96; 95% CI, 1.36-35.77; p = 0.02). rs1130409 was also associated with the time to occurrence of severe RP (p = 0.04). Three-dimensional model APEX1 protein showed that rs1130409 is located in the random coil structure corresponding to the DNA repair function region.
  
  
  CONCLUSIONS
  rs1130409 of APEX1 can be a predictor of RP grades ≥3 among patients with lung cancer.
authors.affiliation: 1 Cancer Center, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Xiong
authors.forename: J
authors.initials: J
authors.lastname: Xian
authors.forename: M
authors.initials: M
authors.lastname: Du
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Liao
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000235:genetics*; D012306:Risk; D012307:Risk Factors
chemical_list: C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase