Harvard Radiation Oncology Program, Boston, MA, USA.
Cancer. 2012 Jul 15;118(14):3654-65. doi: 10.1002/cncr.26667. Epub 2011 Dec 5.
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.
本研究旨在探讨候选基因氧化应激通路中功能性单核苷酸多态性与接受胸部放射治疗的局部晚期肺癌患者放射性肺炎（RP）风险之间的关联。
对 2001 年至 2007 年间接受放射治疗的 136 例肺癌患者进行了回顾性分析，这些患者在接受放射治疗之前进行了候选基因氧化应激基因（包括超氧化物歧化酶 2 [SOD2；rs4880]和亚甲基四氢叶酸还原酶 [MTHFR；rs1801131、rs1801133]）的功能单核苷酸多态性基因分型。使用国家癌症研究所不良事件常用术语标准，版本 4.0 对 RP 事件进行了回顾性评分。使用 Cox 比例风险回归模型分别在单变量和多变量分析中识别与 RP 风险相关的临床变量和基因型，RP 分级为≥2 级和≥3 级。对 P 值进行了多重假设检验校正。
中位随访时间为 21.4 个月，≥2 级 RP 的发生率为 29%，≥3 级 RP 的发生率为 14%。多变量分析调整了同期化疗和巩固多西他赛、肺剂量学参数（如接受>20 Gy 的体积和平均肺剂量）等临床因素后，MTHFR 基因型（rs1801131；AA 与 AC/CC）与≥2 级 RP（风险比：0.37；95%置信区间：0.18-0.76；P=0.006，校正 P=0.018）和≥3 级 RP（风险比：0.21；95%置信区间：0.06-0.70；P=0.01；校正 P=0.03）的风险显著相关。SOD2 基因型与 RP 无关。
本研究表明 MTHFR 基因型与临床上显著的 RP 风险之间存在关联。进一步研究 MTHFR 相关途径可能有助于深入了解 RP 的发病机制。
