Zhou Yu-Ling, Zhang Wen-Cheng, Chen Xia-Bin, Xiao Ze-Fen, Qiao Yan, Yu Dian-Ke, Lin Dong-Xin, Tan Wen
Department of Etiology & Carcinogenesis, State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2011 Jul;45(7):583-7.
To evaluate the association between polymorphism of transforming growth factor-β1 (TGF-β1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients.
The genotype of TGF-β1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox-regression analyses.
Among 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-β1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-β1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-β1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P > 0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively).
These results suggest that TGF-β1-509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients.
评估转化生长因子-β1（TGF-β1）-509C/T基因多态性与食管鳞状细胞癌（ESCC）患者放化疗反应及生存之间的关联。
采用基于聚合酶链反应的限制性片段长度多态性分析（PCR-RFLP）检测230例接受单纯放疗或放化疗联合治疗的ESCC患者的TGF-β1-509C/T基因型。进行无条件多因素逻辑回归分析，以估计该多态性与放化疗反应的校正比值比（OR）及其相应的95%置信区间（CI）。通过单因素和多因素Cox回归分析评估ESCC患者的总生存时间或风险比（HR）与基因变异或临床数据之间的关联。
在208例接受上消化道造影评估的患者中，87例对放化疗敏感，TGF-β1-509CC、CT和TT基因型患者分别为17例（19.5%）、48例（55.2%）和22例（25.3%）。在对放化疗不敏感的患者（n = 121）中，TGF-β1-509CC、CT和TT基因型患者分别为39例（32.2%）、54例（44.6%）和28例（23.2%）。与TGF-β1-509CC基因型相比，CT和TT基因型携带者的治疗反应明显更好（校正OR = 2.07，95%CI，1.05 - 4.09，P = 0.036）。CC基因型患者的中位生存时间为17.0（95%CI，12.0 - 23.0）个月；CT基因型患者为22.0（95%CI，16.0 - 33.0）个月；TT基因型患者为25.0（95%CI，15.0 - 41.0）个月。与CC基因型患者相比，CT和TT组的生存时间差异接近统计学临界点（P = 0.063）。我们的数据显示，与CC基因型相比，CT或TT基因型受试者的HR分别降低（CT，校正HR = 0.81，95%CI，0.52 - 1.24；TT，校正HR = 0.86，95%CI，0.65 - 1.12），但差异无统计学意义（P > 0.05）。然而，肿瘤位置、临床分期和放化疗反应对患者的总生存时间有显著影响（校正HR分别为1.28，95%CI：1.01 - 1.61，P = 0.040；1.49，95%CI，1.17 - 1.88，P = 0.001；1.55，95%CI，1.06 -
