Kim Jong Gwang, Chae Yee Soo, Sohn Sang Kyun, Moon Joon Ho, Ryoo Hun Mo, Bae Sung Hwa, Kum Yoonseop, Jeon Seong Woo, Lim Kyoung-Hoon, Kang Byung-Mo, Park In-Ja, Choi Gyu Seog, Jun Soo-Han
Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Jung-Gu, Daegu, Korea.
Cancer Chemother Pharmacol. 2009 Oct;64(5):953-60. doi: 10.1007/s00280-009-0947-3. Epub 2009 Feb 15.
The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.
A total of 76 patients with recurrent or metastatic colorectal cancer treated with capecitabine and oxaliplatin (XELOX) combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 15 apoptosis-related genes (TP53, BCL2L, TNFRSF10B, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL, caspase 3, and caspase 6-10) were determined using a PCR-RFLP assay.
No significant association between the polymorphisms and the response was found for any of the genes analyzed. However, the T/T genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in a multivariate analysis adjusted for age, sex, performance status, disease status and curative resection. No association was noted between the other polymorphisms and survival.
The PTGS2 8473T>C polymorphism was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX chemotherapy.
本研究分析了凋亡相关基因的多态性及其对结直肠癌患者化疗反应和生存的影响。
本研究共纳入76例接受卡培他滨和奥沙利铂（XELOX）联合化疗的复发或转移性结直肠癌患者。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）法测定15个凋亡相关基因（TP53、BCL2L、TNFRSF10B、AKT1、PTGS2/COX2、BID、RIPK1、FAS、FASL、半胱天冬酶3以及半胱天冬酶6 - 10）的单核苷酸多态性。
在所分析的任何基因中，均未发现多态性与化疗反应之间存在显著关联。然而，在对年龄、性别、体能状态、疾病状态和根治性切除进行校正的多因素分析中，与PTGS2 8473T>C（rs5275）的T/T基因型相比，T/C和C/C基因型组合的无进展生存期（PFS）和总生存期（OS）显著更差（风险比[HR]=0.47；P值=0.046；HR = 0.16；P = 0.013）。未发现其他多态性与生存之间存在关联。
在接受XELOX化疗的晚期结直肠癌患者中，发现PTGS2 8473T>C多态性与PFS和OS相关。
