A polymorphism in the DNA repair domain of APEX1 is associated with the radiation-induced pneumonitis risk among lung cancer patients after radiotherapy.

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-SNaP-shot® (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 >30Gy (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 rs!130409 is located in the random coil structure corresponding to the DNA repair function region. Advances in knowledge: rs1130409 of APEX1 can be a predictor of RP grades ≥3 among patients with lung cancer. [ABSTRACT FROM AUTHOR]