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.
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.
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DOI：
10.1002/cncr.26667
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发表时间：
2012-07-15
期刊：
影响因子：
6.2
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Mak RH;Alexander BM;Asomaning K;Heist RS;Liu CY;Su L;Zhai R;Ancukiewicz M;Napolitano B;Niemierko A;Willers H;Choi NC;Christiani DC
研究氧化应激通路中候选基因的功能性单核苷酸多态性（SNP）与局部晚期肺癌（LC）胸部放射治疗（RT）患者放射性肺炎（RP）风险之间的关联。
我们回顾了2001年至2007年间136例接受RT治疗的LC患者，并对氧化应激基因中的功能性SNP进行了基因分型，这些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）。使用《不良事件通用术语标准》第4.0版对RP事件进行回顾性评分。通过Cox比例风险回归在单变量和多变量分析中确定与≥2级和≥3级RP风险相关的临床变量和基因型。对P值进行多重假设检验校正。
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%。在多变量分析中，在校正了同步化疗、巩固多西他赛等临床因素以及V20和平均肺剂量等肺剂量学参数后，MTHFR基因型（rs1801131；AA与AC/CC相比）与≥2级RP风险显著相关（风险比[HR]：0.37；95%置信区间[CI]：0.18 - 0.76；p = 0.006，校正p = 0.018）以及与≥3级RP风险显著相关（HR：0.21；95%CI：0.06 - 0.70；p = 0.01；校正p = 0.03）。SOD2基因型与RP无关。
我们的研究表明MTHFR基因型与具有临床意义的RP风险之间存在关联。对MTHFR相关通路的进一步研究可能有助于深入了解RP背后的机制。
To study the association between functional single nucleotide polymorphisms (SNPs) in candidate genes from oxidative stress pathways, and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy (RT) for locally advanced lung cancer (LC). We reviewed 136 patients treated with RT for LC between 2001 and 2007, and had prior genotyping of functional SNPs in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylenetetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the 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 grade ≥2 and grade ≥3 RP on univariate and multivariate analysis. P-values were corrected for multiple hypothesis testing. 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 V20 and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of ≥grade 2 RP (Hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18-0.76; p=0.006, corrected p=0.018) and ≥grade 3 RP (HR: 0.21; 95% CI: 0.06-0.70; p=0.01; corrected p=0.03). SOD2 genotype was not associated with RP. Our 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.
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DOI：
10.1016/s0360-3016(01)01685-6
发表时间：
2001-11-01
影响因子：
7
作者：
Hernando, ML;Marks, LB;Lind, PA
通讯作者：
Lind, PA
影响因子：
19.7
作者：
Kim, TH;Cho, KH;Kim, DY
通讯作者：
Kim, DY
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1016/s0360-3016(99)00183-2
发表时间：
1999-09-01
影响因子：
7
作者：
Graham, MV;Purdy, JA;Perez, CA
通讯作者：
Perez, CA
影响因子：
45.3
作者：
Yuan, Xianglin;Liao, Zhongxing;Wei, Qingyi
通讯作者：
Wei, Qingyi