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. 2013 Mar 15;85(4):1066-73.
doi: 10.1016/j.ijrobp.2012.09.024. Epub 2012 Nov 12.

ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy

Huihua Xiong  1 , Zhongxing Liao, Zhensheng Liu, Ting Xu, Qiming Wang, Hongliang Liu, Ritsuko Komaki, Daniel Gomez, Li-E Wang, Qingyi Wei
Affiliations

ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy

Huihua Xiong et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP).

Methods and materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered.

Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites.

Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

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Conflict of interest statement

Conflicts of Interest Notification: The authors declare no conflicts of interest regarding the work presented here.

Figures

Fig. 1
Fig. 1
Cumulative probability of Grade ≥ 3 radiation pneumonitis in 362 patients with non–small cell lung cancer as a function of time from the start of radiation therapy by genotypes: (a) ATM rs189037 AG vs. AA and GG vs. AA, (b) ATM rs228590 CT+TT vs. CC, (c) ATM rs1801516 AG+AA vs. GG, (d) ATM rs189037 G and ATM rs228590 T combined alleles, RP = radiation pneumonitis.
Fig. 2
Fig. 2
Classification and regresion tree analysis for predicators of grade≥3 radiation pneumonitis in 362 patients with non-small cell lung cancer. ATM = ataxia telangiectasia mutated gene; HR = hazard ratio; MLD = mean lung dose; Chemo = chemotherapy.
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