The first 2 authors contributed equally to this work.
A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy
Article first published online: 5 DEC 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 14, pages 3654–3665, 15 July 2012
How to Cite
Mak, R. H., Alexander, B. M., Asomaning, K., Heist, R. S., Liu, C.-y., Su, L., Zhai, R., Ancukiewicz, M., Napolitano, B., Niemierko, A., Willers, H., Choi, N. C. and Christiani, D. C. (2012), A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy. Cancer, 118: 3654–3665. doi: 10.1002/cncr.26667
See editorial on pages 3450–4, this issue.
- Issue published online: 2 JUL 2012
- Article first published online: 5 DEC 2011
- Manuscript Accepted: 6 JUL 2011
- Manuscript Revised: 15 JUN 2011
- Manuscript Received: 11 MAY 2011
- National Institutes of Health. Grant Number: CA 74386
- radiation pneumonitis;
- single-nucleotide polymorphism;
- lung cancer;
- oxidative stress;
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.
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.
With a median follow-up of 21.4 months, the incidence of grade ≥2 RP was 29% and grade ≥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 (rs1801131; 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.
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. Cancer 2012;3654–3665. © 2011 American Cancer Society.