TNF-α promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx

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. What's new? Despite similar pathological features at diagnosis and similar treatments, disease recurrence rates among patients with squamous cell carcinoma of the nonoropharynx (SCCNOP) can vary dramatically. That variation may be attributed to inter-individual genetic differences, a hypothesis supported by this study, in which promoter variants of TNF-α were found to modify recurrence risk in SCCNOP. Three genotypes in particular, TNF-α -857 CC, TNF-α -863 CC, and TNF-α -1031 TT, were associated with poor disease-free survival and high risk of SCCNOP recurrence, especially among smokers and patients who received chemo-radiation therapy.