TNF-? promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx.
Functional polymorphisms of tumor necrosis factor-alpha (TNF-?) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF-? gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF-? 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-? polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF-? -857 CC, TNF-? -863 CC and TNF-? -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-? -308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF-? -857, TNF-? -863 and TNF-? -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-? -857, TNF-? -863 and TNF-? -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.