ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy
Menée sur 362 patients atteints d'un cancer du poumon non à petites cellules traité par radiothérapie, cette étude montre une association entre des polymorphismes du gène ATM et le risque de pneumopathie sévère liée au traitement
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). 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. 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. ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.
International journal of radiation oncology, biology, physics , résumé, 2011