title: TNF-α promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx.
abstract: 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.
authors.affiliation: 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.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhang
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zheng
authors.forename: Mark E
authors.initials: ME
authors.lastname: Zafereo
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: TNF-α variant; biomarkers; genetic polymorphisms; head and neck cancer; recurrence; squamous cell carcinomas of the nonoropharynx