Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Int J Cancer. 2014 Oct 1;135(7):1615-24. doi: 10.1002/ijc.28793. Epub 2014 Feb 27.
Functional polymorphisms of tumor necrosis factor-alpha (TNF-α) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF-α gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF-α polymorphisms and risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP). We used log-rank test and multivariable Cox models to evaluate the associations between TNF-α polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF-α -857 CC, TNF-α -863 CC and TNF-α -1031 TT genotypes had significantly worse disease-free survival (log-rank, p = 0.014, log-rank, p = .020, and log-rank, p = .002, respectively) and higher risk of disease recurrence than patients with the corresponding variant genotypes, respectively (hazard ratio [HR], 1.4, 95% CI, 1.1-1.9, HR, 1.4, 95% CI, 1.0-1.8 and HR, 1.6, 95% CI, 1.2-2.2, respectively). However, no significant association was detected for the TNF-α -308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms with risk of recurrence were more pronounced in smokers and patients treated with chemoradiation. Our findings support a significant role of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms in recurrence of SCCNOP, especially in smokers and patients treated with chemoradiation. Future prospective studies with larger sample size are needed to confirm these findings.
肿瘤坏死因子-α（TNF-α）的功能多态性可能在调节免疫和炎症反应中发挥关键作用，并可能影响 TNF-α 基因的转录水平，从而促进癌症的发生和癌症患者的结局。在一项队列研究中，我们探讨了 TNF-α 多态性与非口咽鳞状细胞癌（SCCNOP）复发风险之间的关系。我们使用对数秩检验和多变量 Cox 模型来评估 TNF-α 多态性与复发风险之间的关系。在总体比较中，TNF-α-857CC、TNF-α-863CC 和 TNF-α-1031TT 基因型的患者无病生存率明显较差（对数秩检验，p=0.014、对数秩检验，p=0.020 和对数秩检验，p=0.002），疾病复发的风险也高于相应的变异基因型患者（风险比[HR]，1.4，95%CI，1.1-1.9，HR，1.4，95%CI，1.0-1.8 和 HR，1.6，95%CI，1.2-2.2）。然而，TNF-α-308 多态性与无病生存率之间没有显著相关性。此外，根据吸烟状况和治疗方法进行进一步分层分析，我们发现 TNF-α-857、TNF-α-863 和 TNF-α-1031 多态性与复发风险的相关性在吸烟者和接受放化疗的患者中更为显著。我们的研究结果支持 TNF-α-857、TNF-α-863 和 TNF-α-1031 多态性在 SCCNOP 复发中的重要作用，尤其是在吸烟者和接受放化疗的患者中。需要进行更大样本量的前瞻性研究来证实这些发现。
