Department of Statistics and Informatics Science, Providence University, Taiwan.
Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1996-2003. doi: 10.1016/j.ijrobp.2011.02.036. Epub 2011 May 17.
To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients.
A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study.
From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined.
This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.
鉴定种系多态性以预测食管癌患者同步放化疗（CCRT）的反应。
本研究共纳入 1997 年至 2008 年期间在台湾大学医院接受 CCRT（基于顺铂的化疗联合 40Gy 放疗）和随后的食管切除术治疗的 139 例食管癌患者。排除混杂因素（即女性和年龄≥70 岁的患者）后，共纳入 116 例患者以鉴定与特定 CCRT 反应相关的单核苷酸多态性（SNP）。利用基因分型阵列和质谱分析，从血液样本中确定种系多态性。这些多态性在疾病进展过程中保持稳定，与肿瘤组织中的体细胞突变不同。本研究采用两阶段设计和加性遗传模型。
在第一阶段鉴定的 26 个 SNP 中，有 2 个 SNP 在第二阶段被发现与 CCRT 反应显著相关。位于染色体 2q36.1 上 SGPP2 和 FARSB 之间的 SNP rs16863886 与 CCRT 病理完全缓解的 3.93 倍增加显著相关（95%置信区间 1.62-10.30），符合加性模型。位于染色体 2q21.3 上的 ZRANB3 中的 SNP rs4954256 与 CCRT 病理完全缓解的 3.93 倍增加相关（95%置信区间 1.57-10.87）。这两个 SNP 联合预测 CCRT 反应的准确率为 71.59%。
这是第一项鉴定种系多态性以高精度预测食管癌 CCRT 反应的研究。
