RGD Reference Report - ATM polymorphisms are associated with risk of radiation-induced pneumonitis. - Rat Genome Database

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ATM polymorphisms are associated with risk of radiation-induced pneumonitis.

Authors: Zhang, Li  Yang, Ming  Bi, Nan  Fang, Mingjing  Sun, Tong  Ji, Wei  Tan, Wen  Zhao, Lujun  Yu, Dianke  Lin, Dongxin  Wang, Luhua 
Citation: Zhang L, etal., Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1360-8. doi: 10.1016/j.ijrobp.2009.07.1675. Epub 2010 Feb 18.
RGD ID: 150340755
Pubmed: (View Article at PubMed) PMID:20171797
DOI: Full-text: DOI:10.1016/j.ijrobp.2009.07.1675

PURPOSE: Since the ataxia telangiectasia mutated (ATM) protein plays crucial roles in repair of double-stranded DNA breaks, control of cell cycle checkpoints, and radiosensitivity, we hypothesized that variations in this gene might be associated with radiation-induced pneumonitis (RP).
METHODS AND MATERIALS: A total of 253 lung cancer patients receiving thoracic irradiation between 2004 and 2006 were included in this study. Common Terminology Criteria for Adverse Events version 3.0 was used to grade RP. Five haplotype-tagging single nucleotide polymorphisms (SNPs) in the ATM gene were genotyped using DNA from blood lymphocytes. Hazard ratios (HRs) and 95% confidence intervals (CIs) of RP for genotypes were computed by the Cox model, adjusted for clinical factors. The function of the ATM SNP associated with RP was examined by biochemical assays.
RESULTS: During the median 22-month follow-up, 44 (17.4%) patients developed grade > or = 2 RP. In multivariate Cox regression models adjusted for other clinical predictors, we found two ATM variants were independently associated with increased RP risk. They were an 111G > A) polymorphism (HR, 2.49; 95% CI, 1.07-5.80) and an ATM 126713G > A polymorphism (HR, 2.47; 95% CI, 1.16-5.28). Furthermore, genotype-dependent differences in ATM expression were demonstrated both in cell lines (p < 0.001) and in individual lung tissue samples (p = 0.003), which supported the results of the association study.
CONCLUSIONS: Genetic polymorphisms of ATM are significantly associated with RP risk. These variants might exert their effect through regulation of ATM expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)

Additional Information