Abstract
TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility. HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma (OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic white population, and used logistic regression models to evaluate the joint effects on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6-960.4) or never-drinkers (OR, 196.0; 95% CI, 28.2-1,000.0), respectively. Younger subjects had a higher risk of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3-87.0 vs. OR, 6.0; 95% CI, 1.7-17.9, respectively). The significant associations between this polymorphism and HPV16-associated OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results. Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects who are never-smokers, never-drinkers and young. This result may help us understand the tumorigenesis process and improve early detection, which are critical for prevention and intervention strategies. However, larger studies are needed to validate our findings.
Highlights
Oral squamous cell carcinoma (OSCC) consists of oral cavity squamous cell carcinoma (OCSCC) and oropharynx squamous cell carcinoma (OPSCC)[1,2]
When HPV16 serology was taken into account, and the effects were adjusted for age, sex, and smoking/drinking status, we found that HPV16 seronegative individuals carrying the TT genotype of TGF-β1rs1982073 had the lowest risk
We evaluated the association between the TGF-β1rs1982073 genotype and HPV16 L1 serology in 325 non-Hispanic white OSCC patients and 335 cancer-free controls, and found that TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1seropositivity increased the risk of OSCC via joint effects, most notably in OPSCC subjects who were never-smokers or never-drinkers, respectively
Summary
Oral squamous cell carcinoma (OSCC) consists of oral cavity squamous cell carcinoma (OCSCC) and oropharynx squamous cell carcinoma (OPSCC)[1,2]. TGF-β1, a member of the TGF-β family, suppresses tumorigenesis in precancerous tissues and promotes invasiveness in advanced tumors, mainly owing to disequilibrium of TGF-β1 signaling, which features interwoven pathways with complex cross-talk and highly contextual dependence 8. TGF-β1rs1982073 located at the miR-187 binding sites and the binding minimum free energy (MFE) were modified in the duplex of miR-187::TGFB1-mRNA by the T to C transition of TGF-β1rs1982073. This binding modification can alter miRNA gene regulation and TGF-β1 expression and function and thereby affect the risk of cancer 12
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