Genetic variants inTNF-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.

Parotid gland lesions: separate and combined diagnostic value of conventional MRI, diffusion-weighted imaging and dynamic contrast-enhanced MRI

“…Patients who had smoked at least 100 cigarettes in their lifetime were defined as "ever smokers". 5 Patients were excluded in any of the following conditions: (1) a head and neck cancer was previously diagnosed; (2) surgical management or radiotherapy treatment in head and neck region was performed; or (3) the parotid lesion received biopsy, surgery, chemotherapy or radiotherapy. This study was approved by the institutional review board.…”

Epidemiology of HPV-associated oropharyngeal cancer

“…28 Other known risk factors for the development of OPSCC, such as genetic polymorphisms, may also predispose patients to the development of HPV positive OPSCC as well as decrease survival. 29, 30 Further studies need to be completed to examine cofoactors of malignant transformation in patients with HPV positive OPSCC.…”

Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy

“…All subjects signed an informed consent form that had been approved by the institutional review board of The University of Texas MD Anderson Cancer Center (Houston, Texas). The more details of patients' follow-up and clinical data were previously described [39, 40]. In this study, we clearly defined and distinguished the recurrence from second primary tumors to minimize the over- or underestimation of associations.…”