ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

作者：Xiong Huihua; Liao Zhongxing; Liu Zhensheng; Xu Ting; Wang Qiming; Liu Hongliang; Komaki Ritsuko; Gomez Daniel; Wang Li E; Wei Qingyi^*

来源：International Journal of Radiation Oncology, Biology, Physics, 2013, 85(4): 1066-1073.

DOI：10.1016/j.ijrobp.2012.09.024

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). %26lt;br%26gt;Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G%26gt;A], rs189037 [-111G%26gt;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. %26lt;br%26gt;Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade %26gt;= 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. %26lt;br%26gt;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.

• 出版日期2013-3-15
• 单位华中科技大学