A Single-Nucleotide Polymorphism in the Mthfr (Methylene Tetrahydrofolate Reductase) Gene Is Associated with Risk of Radiation Pneumonitis in Lung Cancer Patients Treated with Thoracic Radiation Therapy
Resource
CANCER pp.EPUB
Journal
CANCER
Pages
EPU-B
Date Issued
2011
Date
2011
Author(s)
LIU, CHEN-YU
Abstract
BACKGROUND: This study examined the association between functional single -nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer. METHODS: A review was conducted of 136 patients treated with radiation therapy for lung cancer between 2001 and 2007, and who had prior genotyping of functional single-nucleotide polymorphisms in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylene tetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of RP of grades ≥2 and ≥3 on univariate and multivariate analysis, respectively. P values were corrected for multiple hypothesis esting. RESULTS: With a median follow-up of 21.4 months, the incidence of grade ≥ 8805;2 RP was 29% and grade 8805;3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy and consolidation docetaxel, and lung dosimetric parameters such as volume receiving greater than 20 Gy and mean lung dose, MTHFR genotype (rs 1801131; AA versus AC/CC) was significantly associated with risk of grade ≥2 RP (hazard ratio: 0. 37; 95% confidence interval: 0.18-0.76; P = .006, corrected P = .018 ) and grade ≥3 RP (hazard ratio: 0.21; 95% confidence interval: 0.06-0.70 ; P = .01; corrected P = .03). SOD2 genotype was not associated with RP. CONCLUSIONS: This study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR-related pathways may provide insight into the mechanisms behind RP.
Subjects
radiation pneumonitis
single-nucleotide polymorphism
lung cancer
oxidative stress
MTHFR
SDGs