Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China.
Clin Cancer Res. 2010 Feb 15;16(4):1236-44. doi: 10.1158/1078-0432.CCR-09-2719. Epub 2010 Feb 9.
Disruption of the balance of insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP3) has been implicated in the etiology and progression of lung and other cancers. Single nucleotide polymorphisms (SNP) in IGF1 and IGFBP3 have been reported to be associated with the expression of the IGF-I/IGFBP3 axis. Therefore, we hypothesized that SNPs in these two genes were associated with lung cancer survival.
We selected and genotyped 21 tagging and potentially functional SNPs in IGF1 and IGFBP3 by using Illumina Goldengate Genotyping Chip in a case cohort of 568 patients diagnosed with non-small cell lung cancer (NSCLC) in a Chinese population. Log-rank test and Cox proportional hazard models were used for the survival analyses.
We found that rs5742714C/G in the 3'-untranslated region of IGF1 was associated significantly with NSCLC survival after adjustment for demographic and clinicopathologic factors, showing an improved median survival time in patients carrying variant CG/GG genotypes [median survival time, 28.5 months for CG/GG and 23.0 for CC; crude hazard ratio (HR), 0.74; 95% confidence interval (95% CI), 0.57-0.95, and adjusted HR, 0.77; 95% CI, 0.60-0.99]. This protective effect was more predominant for patients receiving surgical operation (HR, 0.58; 95% CI, 0.40-0.85; P for heterogeneity test = 0.045), along with a significant multiplicative interaction between variant genotypes and operation status (P = 0.028).
Our findings suggest that rs5742714 in IGF1 may be a genetic modifier for NSCLC prognosis in this Chinese population, especially among patients with surgical operation.
胰岛素样生长因子 I（IGF-I）和 IGF 结合蛋白 3（IGFBP3）平衡的破坏与肺癌和其他癌症的病因和进展有关。已经报道 IGF1 和 IGFBP3 中的单核苷酸多态性（SNP）与 IGF-I/IGFBP3 轴的表达有关。因此，我们假设这两个基因中的 SNP 与肺癌的生存有关。
我们通过使用 Illumina Goldengate 基因分型芯片，在中国人群中对非小细胞肺癌（NSCLC）诊断为 568 例患者的病例队列中选择并对 IGF1 和 IGFBP3 中的 21 个标记和潜在功能 SNP 进行基因分型。对数秩检验和 Cox 比例风险模型用于生存分析。
我们发现 IGF1 的 3'-非翻译区中的 rs5742714C/G 与 NSCLC 生存显著相关，调整了人口统计学和临床病理因素后，携带变异 CG/GG 基因型的患者中位生存时间得到改善[中位生存时间，CG/GG 为 28.5 个月，CC 为 23.0 个月；粗危险比（HR），0.74；95%置信区间（95%CI），0.57-0.95，和调整后的 HR，0.77；95%CI，0.60-0.99]。对于接受手术治疗的患者，这种保护作用更为明显（HR，0.58；95%CI，0.40-0.85；P 异质性检验=0.045），同时变异基因型与手术状态之间存在显著的乘法交互作用（P=0.028）。
我们的研究结果表明，IGF1 中的 rs5742714 可能是该中国人群中 NSCLC 预后的遗传修饰因子，尤其是在接受手术治疗的患者中。
