Prognostic value of transforming growth factor beta receptor 1 polymorphisms in patients with oral cancer

Abstract

Objective: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1). Methods:Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer.Results: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed.Conclusions: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings. K E Y W O R D Soral cancer, prospective study, radiotherapy, TGFBR1

TGF-β1 and TGF-βR1 variants are associated with clinical outcomes in smoking-related head and neck cancer patients treated with chemoradiation through modulating microRNA-mediated regulation

“…Knobloch et al [ 31 ] identified a significant association between TGF-βR1 rs334348 and both the occurrence and advancement of HNSCC. Chen et al [ 32 ] discovered that the TGF-βR1 rs334348 polymorphism may modulate the progression of oral cancer by regulating the expression of TGF-βR1 and diminishing its ability to phosphorylate Smad-2 and Smad-3. Moreover, the researchers detected a synergistic association between TGF-βR1 rs334348 GA or GG genotype and the improved DSS of patients treated with radiotherapy, implying the potential clinical relevance of this genetic alteration in cancer management.…”

Decorin inhibits proliferation and metastasis in human bladder cancer cells by upregulating P21

“…[ 30 ] It may act as a tumor suppressor gene during tumor development and progression. [ 31 ] It is a highly specific in vivo inhibitor of TGF-β as decorin and biglycan bind to and inhibit TGF-β activity. [ 32 ] It sequesters and reduces the stromal bioavailability of TGF-β, which is therefore incapable of initiating downstream signaling.…”

Clinical Implications of Single Nucleotide Polymorphisms in Oral Cancer

“…FADS1 rs174549 is determined to be a potentially independent and favorable factor in predicting oral cancer PFS HR-0.52 (95% CI: 0.29-0.93) for patients with CCRT (Table 1) [34]. TGFBR1 plays a critical role in the TGF-β/ SMAD signaling pathway vital in the development and progression of cancer by regulating cellular proliferation and differentiation [42]. The TGFBR1 rs33438 polymorphism is associated with a low risk of death due to oral cancer in codominant (AG vs AA: HR=0.55, 95% CI=0.35-0.88) and dominant (GG+AG vs AA: HR=0.57, 95% CI=0.38-0.87) models.…”

“…Moreover, better disease specific survival (DSS) (GG+AG vs AA: HR=0.50, 95% CI=0.29-0.85) was reported in patients given radiotherapy. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P=0.001) (Table 1) [42]. TGFBR1 rs334348 polymorphism may influence the progression of oral cancer by regulating the levels of TGFBR1 and inhibiting its function of phosphorylating Smad-2 and Smad-3 and consequent increased cell proliferation, a hallmark of cancer [42].…”