title: Genetic variants in TNF-α promoter are predictors of recurrence in patients with squamous cell carcinoma of oropharynx after definitive radiotherapy.
abstract: The promoter variants of TNF-α, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF-α promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated associations of four TNF-α polymorphisms with risk of recurrence in a cohort of 846 patients with SCCOP. Log-rank test and multivariable Cox models were used to evaluate associations. Compared with patients with variant genotypes of the TNF-α -308 and TNF-α -863 polymorphisms, patients with common homozygous genotypes had worse disease-free survival (log-rank p = 0.0002 and p < 0.0001, respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3-2.8 and HR, 1.9, 95% CI, 1.3-2.7, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of the TNF-α -308 and -863 polymorphisms had worse disease-free survival (log-rank p = 0.005 and p = 0.007, respectively) and higher recurrence risk than patients with variant genotypes of these polymorphisms (HR, 5.1, 95% CI, 1.4-18.4 and HR, 3.7, 95% CI, 1.5-9.1, respectively), while no such significant associations were found for TNF-α -857 or -1031 polymorphisms. Our findings suggest that TNF-α -308 and -863 polymorphisms may modulate the risk of SCCOP recurrence in patients with HPV16-positive tumors. However, larger studies are needed to validate these results.
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: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Li
authors.initials: L
authors.lastname: Chao
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000532:radiotherapy; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D030361:Papillomavirus Infections / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha
keywords: TNF-α variant; biomarkers; genetic polymorphisms; head and neck cancer; human papillomavirus; oropharyngeal cancer; recurrence