Cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. Transforming growth factor-beta 1 (TGF-β1) plays a significant role in regulating the proliferation and apoptosis of epithelial cells. Interleukin 10 (IL-10) is an immunoregulatory cytokine with biological functions of anti-inflammation, immunosuppression, allergy, and anti-agenesis. The two cytokines are supposed to play an important role in carcinogenesis. The association between cytokine gene polymorphisms with oral cancer (OC) was investigated. We studied the association between the polymorphism in TGF-β1 (G to C polymorphism at codon 25 <+915>) and IL-10 (-1082 G/A, -819 C/T, and -592 C/A) and the risk of OC in patients (n = 162) and healthy controls (n = 118) in Taiwan. All genotyping experiments were performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method. It was found that the codon 25 GC genotype of TGF-β1 is significantly higher in frequency in patients with OC compared with a healthy control group (p < 0.0001). People with the GC genotype in codon 25 had an 11.09-fold increased risk of OC [odds ratio (OR) = 11.09; 95% confidence interval (CI) = 6.16-113.23]. IL-10 polymorphisms in -819 and -592 positions correlated with the risk of OC (p < 0.0001). The IL-10 -592 C allele-containing genotypes posed an increased risk of OC (OR = 1.79, 95% CI = 1.11-2.91). People with the CT genotype in IL-10 -819 had a 3.32-fold increased risk of OC (OR = 3.32; 95% CI = 1.64-6.94). The results suggest that polymorphisms in TGF-β1 and IL-10 may have a significant influence on the development of OC.

Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs). Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN)-γ, transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A), TGF-β1 (codons 10 T/C and 25 G/C), TNF-α (-308 G/A), IL-6 (-174 G/C), and IL-10 (-1082 A/G, -819 T/C, and -592 A/C)]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ(2)) test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (-308) polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004). Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25) polymorphism was also significantly associated with OPCLs (p < 0.001). The IL-6 polymorphism was significantly associated with OPCLs. There are significant differences in the distribution of CC, GC, and GG genotypes between OPCL patients and controls (p < 0.001). Patients with the CC or GC genotype had a 35- or 20.59-fold increased risk of OPCLs. There were no significant differences in the distribution of IL-10 and IFN-γ genotypes between different groups of control individuals and OPCL patients. The IL-6, TGF-β1, and TNF-α gene polymorphisms may have a significant association with the development of OPCLs.

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Chemotherapy resistance is one of the major challenges in the treatment of liver cancer (LC). The present study aimed to investigate the potential roles of Yes-associated protein (YAP), the core component of the Hippo signaling pathway, in chemoresistance of LC. YAP expression and its function in chemoresistance of LC cells were investigated. It was revealed that the expression levels and nuclear localization of YAP were increased in cisplatin (CDDP)-resistant LC (LC/CDDP) cells. The targeted inhibition of YAP using small interfering RNA or an inhibitor restored the CDDP sensitivity of LC cells. YAP overexpression was discovered to be essential for the increase of IL-6 and TGF-β expression levels in LC/CDDP cells. Furthermore, it was identified that increased mRNA stability was the primary reason for the upregulation of YAP expression in LC/CDDP cells, which was due to the downregulation of microRNA (miR)-375 expression in LC/CDDP cells. In conclusion, the findings of the present study suggested that the miR-375/YAP axis may regulate the expression levels of IL-6 and TGF-β, which may subsequently be involved in the CDDP resistance of LC cells. The current results indicated that the targeted inhibition of this axis and signaling pathway may be helpful in overcoming CDDP resistance.

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