Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiotherapy
Single Nucleotide Polymorphism at rs1982073:T869C of the TGFβ1 Gene Is Associated With the Risk of Radiation Pneumonitis in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiotherapy
复制标题
DOI：
10.1200/jco.2008.20.6763
复制
发表时间：
2009-07-10
影响因子：
45.3
通讯作者：
Wei, Qingyi
中科院分区：
文献类型：
--
作者：
Yuan, Xianglin;Liao, Zhongxing;Wei, Qingyi
目的
为了寻找可靠的生物学标志物，以便在治疗前预测放射（化学）疗法对正常组织损伤的风险，我们研究了转化生长因子β1（TGFβ1）基因的单核苷酸多态性（SNPs）与非小细胞肺癌（NSCLC）患者放射性肺炎（RP）风险之间的关联。
患者与方法
利用164份来自接受根治性放射（化学）疗法治疗的NSCLC患者的可用基因组DNA样本，我们通过聚合酶链反应 - 限制性片段长度多态性方法对TGFβ1基因的三个SNP（rs1800469：C - 509T，rs1800471：G915C和rs1982073：T869C）进行基因分型。我们使用卡普兰 - 迈耶累积概率评估≥3级RP的风险，并使用考克斯比例风险分析评估TGFβ1基因型对该风险的影响。
结果
研究中有90名男性和74名女性，中位年龄为63岁。158名患者（96.3%）接受了60 - 70 Gy（中位值 = 63 Gy）、30 - 58分次的放射剂量，147名患者（89.6%）接受了以铂类为基础的化疗。分别有74名（45.1%）和36名患者（22.0%）观察到≥2级和≥3级RP。多变量分析发现，在对卡氏功能状态、吸烟状况、肺功能和剂量学参数进行调整后，与TT基因型相比，TGFβ1 rs1982073：T869C的CT/CC基因型与≥2级（风险比[HR] = 0.489；95%置信区间，0.227 - 0.861；P = 0.013）和≥3级（HR = 0.390；95%置信区间，0.197 - 0.774；P = 0.007）RP的风险在统计学上显著降低相关。
结论
我们的结果表明，在接受根治性放射（化学）疗法治疗的NSCLC患者中，TGFβ1 rs1982073：T869C基因的CT/CC基因型与较低的RP风险相关，因此可能作为RP的可靠预测因子。
PurposeIn search of reliable biologic markers to predict the risk of normal tissue damage by radio(chemo) therapy before treatment, we investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor 1 (TGF beta 1) gene and risk of radiation pneumonitis (RP) in patients with non-small-cell lung cancer (NSCLC).Patients and MethodsUsing 164 available genomic DNA samples from patients with NSCLC treated with definitive radio( chemo) therapy, we genotyped three SNPs of the TGF beta 1 gene (rs1800469: C-509T, rs1800471:G915C, and rs1982073:T869C) by polymerase chain reaction restriction fragment length polymorphism method. We used Kaplan-Meier cumulative probability to assess the risk of grade >= 3 RP and Cox proportional hazards analyses to evaluate the effect of TGF beta 1 genotypes on such risk.ResultsThere were 90 men and 74 women in the study, with median age of 63 years. Radiation doses ranging from 60 to 70 Gy (median = 63 Gy) in 30 to 58 fractions were given to 158 patients (96.3%) and platinum-based chemotherapy to 147 (89.6%). Grade >= 2 and grade >= 3 RP were observed in 74 (45.1%) and 36 patients (22.0%), respectively. Multivariate analysis found CT/CC genotypes of TGF beta 1 rs1982073:T869C to be associated with a statistically significantly lower risk of RP grades >= 2 (hazard ratio [HR] = 0.489; 95% CI, 0.227 to 0.861; P = .013) and grades >= 3 (HR = 0.390; 95% CI, 0.197 to 774; P = 0.007), respectively, compared with the TT genotype, after adjustment for Karnofsky performance status, smoking status, pulmonary function, and dosimetric parameters.ConclusionOur results showed that CT/CC genotypes of TGF beta 1 rs1982073:T869C gene were associated with lower risk of RP in patients with NSCLC treated with definitive radio(chemo)therapy and thus may serve as a reliable predictor of RP.