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Related Experiment Video

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Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity
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Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation

Jose Luis Lopez Guerra1,2, Yi-Peng Song1,3, Quynh-Nhu Nguyen1

  • 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Chronic Diseases and Translational Medicine
|May 15, 2018
PubMed
Summary
This summary is machine-generated.

Single nucleotide polymorphisms (SNPs) in the ATM gene, specifically the AA genotype of rs189037, are linked to reduced lung diffusing capacity after lung cancer radiotherapy. This genetic marker may indicate a higher risk of lung injury in non-small cell lung cancer patients.

Keywords:
Ataxia telangiectasia-mutated geneNon–small-cell lung cancerRadiation therapySingle-nucleotide polymorphisms

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Area of Science:

  • Oncology
  • Genetics
  • Pulmonology

Background:

  • Single-nucleotide polymorphisms (SNPs) in the ataxia telangiectasia-mutated (ATM) gene are associated with pneumonitis following lung cancer radiotherapy.
  • The impact of ATM gene SNPs on pulmonary function, specifically diffusing capacity of the lung for carbon monoxide (DLCO), remains under-investigated.

Purpose of the Study:

  • To investigate the association between specific SNPs in the ATM gene and changes in DLCO in patients with non-small cell lung cancer (NSCLC) undergoing radiotherapy.
  • To determine if genetic variations in ATM influence the risk of pulmonary function impairment post-radiotherapy.

Main Methods:

  • A cohort of 100 patients with inoperable primary NSCLC who received definitive radiotherapy (≥60 Gy) were analyzed.
  • Two ATM SNPs (rs189037 and rs228590), previously linked to radiation pneumonitis, were genotyped.
  • Logistic regression analysis was used to correlate SNP genotypes with decreases in DLCO post-radiotherapy.

Main Results:

  • The AA genotype of ATM rs189037 was significantly associated with a decrease in DLCO after radiotherapy compared to GG/AG genotypes (multivariate P=0.038).
  • No significant correlation was found between ATM rs228590 and DLCO changes post-radiotherapy (P=0.096).

Conclusions:

  • The AA genotype of ATM rs189037 is associated with an increased risk of lung injury, indicated by reduced DLCO, in NSCLC patients treated with radiotherapy.
  • Prospective validation in diverse patient populations is recommended to confirm these findings.