Chen Yusheng, Shao Hui, Li Hongru, Han Lili, Zhang Xiang'e
Fujian Provincial Medical College, Fujian Medical University, Fuzhou 350001, China.
Zhongguo Fei Ai Za Zhi. 2012 Feb;15(2):65-71. doi: 10.3779/j.issn.1009-3419.2012.02.01.
It has been proven that the insulin-like growth factor 1 receptor (IGF-1R) gene is an important regulator of many aspects of growth, differentiation, and development. The insulin-like growth factor 2 receptor (IGF-2R) gene is a negative mediator for carcinogenesis. The aim of this study is to investigate the relationship of IGF-1R+1013(G/A) and IGF-2R+1619(G/A) single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC).
A total of 132 patients with NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated after four cycles of chemotherapy. IGF-1R+1013(G/A) and IGF-2R+1619(G/A) were genotyped using polymerase chain reaction-restrictive fragment length polymorphism. The relationship between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) genotypes and the clinical benefit rate, as well as the median survival time (MST), was analyzed.
No significant association was found between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) polymorphisms with clinical benefit (P>0.05). Further, we found that the two SNPs could not work together (P=0.975). The MST of patients with IGF-1R+1013(G/A) genotypes with A allele (GA+AA) was significantly shorter than that of GG genotype carriers (P=0.017). There was no significant difference in MST in patients with IGF-2R+1619(G/A) A allele (GA+AA) carrier and GG genotype carrier (P=0.575). The two SNPs showed a synergistic effect on MST. Patients who carried a mutant allele A of IGF-1R+1013(G/A) and a mutant allele A of IGF-2R+1619(G/A) had a MST of 12 months, which was significantly shorter than that of patients with other genotypes (P<0.05). Estimation by the Cox proportional hazards model showed that IGF-1R+1013(G/A) polymorphism is an independent prognostic factor (P=0.020), and IGF-1R+1013(G/A) polymorphism in combination with IGF-2R +1619(G/A) polymorphism is an independent prognostic factor in advanced NSCLC (P=0.025).
IGF-1R+1013(G/A) polymorphism alone or in combination with IGF-2R +1619(G/A) polymorphism was associated with the overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy, which might be a prognostic factor in platin-treated patients with advanced NSCLC.
已证实胰岛素样生长因子1受体（IGF-1R）基因是生长、分化和发育诸多方面的重要调节因子。胰岛素样生长因子2受体（IGF-2R）基因是致癌作用的负向调节因子。本研究旨在探讨IGF-1R +1013（G/A）和IGF-2R +1619（G/A）单核苷酸多态性（SNP）与晚期非小细胞肺癌（NSCLC）铂类化疗疗效的关系。
132例NSCLC患者接受常规铂类化疗，化疗4个周期后评估其临床反应。采用聚合酶链反应-限制性片段长度多态性方法对IGF-1R +1013（G/A）和IGF-2R +1619（G/A）进行基因分型。分析IGF-1R +1013（G/A）和IGF-2R +1619（G/A）基因型与临床获益率以及中位生存时间（MST）之间的关系。
未发现IGF-1R +1013（G/A）和IGF-2R +1619（G/A）多态性与临床获益之间存在显著关联（P>0.05）。此外，发现这两个SNP不能共同起作用（P = 0.975）。携带IGF-1R +1013（G/A）基因型A等位基因（GA + AA）的患者的MST显著短于GG基因型携带者（P = 0.017）。携带IGF-2R +1619（G/A）A等位基因（GA + AA）的患者与GG基因型携带者的MST无显著差异（P = 0.575）。这两个SNP对MST显示出协同作用。携带IGF-1R +1013（G/A）突变等位基因A和IGF-2R +1619（G/A）突变等位基因A的患者的MST为12个月，显著短于其他基因型患者（P<0.05）。Cox比例风险模型估计显示，IGF-1R +1013（G/A）多态性是独立的预后因素（P = 0.020），IGF-1R +1013（G/A）多态性与IGF-2R +1619（G/A）多态性联合是晚期NSCLC的独立预后因素（P = 0.025）。
IGF-1R +l013（G/A）多态性单独或与IGF-2R +1619（G/A）多态性联合与晚期NSCLC患者铂类化疗后的总生存期相关，这可能是铂类治疗的晚期NSCLC患者的一个预后因素。
