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.

Duke Scholars

Author Qingyi Wei Population Health Sciences