Functional Genetic Variants in TGFb1 and TGFbR1 in miRNA-Binding Sites Predict Outcomes in Patients with HPV-positive Oropharyngeal Squamous Cell Carcinoma

Purpose: TGFb1 and TGFb receptor 1 (TGFbR1) participate in DFS compared with patients with AA genotype. Furthermore, regulation of the host’s immune system and inflammatory among patients with HPV-positive (HPV^þ) OPSCC, the same responses and may serve as prognostic biomarkers for human patterns were observed but the risk reductions were greater: up to papillomavirus (HPV)-associated oropharyngeal squamous cell 80%–90% for TGFb1 rs1800470 CT or CC genotype and 70%–85% carcinoma (OPSCC). for TGFbR1 rs334348 GA or GG genotype. The risk reductions were Experimental Design: This study included 1,013 patients with still greater (up to 17 to 25 times reduced) for patients with both incident OPSCC, of whom 489 had tumor HPV16 status deterTGFb1 rs1800470 CT or CC genotype and TGFbR1 rs334348 GA or mined. All patients were genotyped for two functional polymorphGG genotype compared with patients with both TGFb1 rs1800470 isms: TGFb1 rs1800470 and TGFbR1 rs334348. Univariate and TT genotype and TGFbR1 rs334348 AA genotype among patients multivariate Cox regression models were performed to evaluate with HPV^þ OPSCC. associations between the polymorphisms and overall survival (OS), Conclusions: Our findings indicate that TGFb1 rs1800470 and disease-specific survival (DSS), and disease-free survival (DFS). TGFbR1 rs334348 may individually or jointly modify risks of death Results: Patients with TGFb1 rs1800470 CT or CC genotype had and recurrence in patients with OPSCC, particularly those with 70%–80% reduced risks of OS, DSS, and DFS compared with HPV^þ OPSCC undergoing definitive radiotherapy, and may serve patients with TT genotype, and patients with TGFbR1 rs334348 as prognostic biomarkers, which could lead to better personalized GA or GG genotype had 30%–40% reduced risk of OS, DSS, and treatment and improved prognosis.