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SNP in MTHFR Tied to Risk of Radiation Pneumonitis

Significant link seen for patients treated with thoracic radiation for locally advanced lung cancer

FRIDAY, Dec. 16 (HealthDay News) -- In patients treated with thoracic radiation therapy for locally advanced lung cancer, a single-nucleotide polymorphism (SNP) in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with a clinically significant risk of radiation pneumonitis (RP), according to a study published online Dec. 5 in Cancer.

Raymond H. Mak, M.D., from the Harvard Radiation Oncology Program in Boston, and colleagues investigated the association between functional SNPs in genes from oxidative stress pathways and the risk of RP in 136 patients treated with thoracic radiation for locally advanced lung cancer between 2001 and 2007. The participants had previously undergone genotyping of functional SNPs in oxidative stress genes, including superoxide dismutase 2 (SOD2; rs4880) and MTHFR (rs1801131, rs1801133), and were followed up for a median of 21.4 months. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, was used to retrospectively score the RP events. Clinical variables and genotypes associated with the risk of RP of grade ≥2 on univariate, and of grade ≥3 on multivariate analysis, were identified.

The investigators found that the incidence of grades ≥2 and ≥3 RP was 29 and 14 percent, respectively. Multivariate analysis revealed a significant association between MTHFR genotype (rs1801131; AA versus AC/CC) and risk of RP of grades ≥2 and ≥3 (hazard ratios, 0.37 and 0.21 respectively), after adjusting for clinical factors (concurrent chemotherapy and consolidation docetaxel) and lung dosimetric parameters (volume receiving greater than 20 Gray and mean lung dose). No association was seen for SOD2 genotype and RP.

"This study showed an association between MTHFR genotype and risk of clinically significant RP," the authors write.

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