Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA.
BMC Cancer. 2011 Oct 14;11:447. doi: 10.1186/1471-2407-11-447.
The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy.
We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629) and -1031 T>C (rs1799964); TNFRSF1B +676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).
We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N2-3 vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T3-4 vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03).
Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.
TNF-TNFR 超家族中基因表达的失调与包括非小细胞肺癌（NSCLC）在内的多种人类癌症有关。此外，改变基因表达的 TNF-α 和 TNFRSF1B 基因中的功能性多态性，可能与癌症的风险和临床结局有关。然而，很少有研究报道过 TNF-α 和 TNFRSF1B 中潜在功能 SNP 与接受放化疗的 NSCLC 患者预后之间的关系。
我们对 225 例接受放化疗或单纯放疗的 NSCLC 患者的 TNF-α 和 TNFRSF1B 基因的五个潜在功能 SNP（TNF-α-308 G>A(rs1800629) 和 -1031 T>C(rs1799964)；TNFRSF1B+676 T>G(rs1061622)、-1709A>T(rs652625)和+1663A>G(rs1061624)）进行了基因分型。Kaplan-Meier 生存分析、对数秩检验和 Cox 比例风险模型用于评估这些变体与 NSCLC 总生存期（OS）之间的关系。
我们发现 TNFRSF1B+676 GG 基因型与 NSCLC 的 OS 显著相关（GG 与 TT：调整 HR = 0.38，95%CI = 0.15-0.94；GG 与 GT/TT：调整 HR = 0.35，95%CI = 0.14-0.88）。进一步的逐步多变量 Cox 回归分析显示，在 NSCLC 队列中，TNFRSF1B+676 GG 是一个独立的预后预测因子（GG 与 GT/TT：HR = 0.35，95%CI = 0.14-0.85），在淋巴结状态（N2-3 与 N0-1：HR = 1.60，95%CI = 1.09-2.35）和肿瘤分期（T3-4 与 T0-2：HR = 1.48，95%CI = 1.08-2.03）的情况下。
尽管该 SNP 的确切生物学功能仍有待探索，但我们的研究结果表明 TNFRSF1B+676 T>G(rs1061622) 可能在 NSCLC 的预后中起作用。需要进一步的大规模和功能研究来证实我们的发现。
