Role of cytokine gene (interferon‐γ, transforming growth factor‐β1, tumor necrosis factor‐α, interleukin‐6, and interleukin‐10) polymorphisms in the risk of oral precancerous lesions in Taiwanese

Abstract

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.

Association of genetic polymorphisms in interferon-γ, interleukin-6 and transforming growth factor-β1 gene with oral lichen planus susceptibility

“…In accordance with our results, a study from Italy also repoted no significant difference in the allele or genotype frequencies of TGF-β1 between the OLP subjects and healthy controls [26]. Recently Hsu et al [16] suggested that polymorphism in TGF-β 1 (C/T) (rs1800469) is not associated with OPCLs but another polymorphism TGF-β 1 (C/G) at codon 25 is associated significantly with the development of OPCLs in Taiwanese.…”

“…Recently the IL-6 (174G/C) polymorphism has also been significantly associated with oral precancerous lesions (OPCLs) in Taiwanese patients [16]. These differences in the results can be attributed to the ethnic variations in the distribution of polymorphic variants as the genotypes/alleles frequencies of polymorphisms are known to vary according to race or ethnicity.…”

“…These polymorphisms consist of a single nucleotide change from guanine (G) to cytosine (C) at positions −572 and −174 in the promoter region, respectively [14, 15]. Some researchers have investigated a possible association between IL-6 (−174G/C) polymorphism and OLP in Taiwanese and Brazilian patients [16, 17]. …”

Meta-analysis of the role of IL-6 rs1800795 polymorphism in the susceptibility to prostate cancer

“…[6] Existing documents have demonstrated that among material bases for genetic susceptibility to prostate cancer, single-nucleotide polymorphism (SNP) presents a key one. [7] …”

Association between polymorphisms in interleukins and oral lichen planus

“…[15,16] More and more studies suggested that SNPs in interleukins genes, such as IL4 (−590T/C, −1098T/G), IL6 (−174G/C), IL10 (−592C/A, −819C/T, and −1082G/A), and IL18 (−137G/C, −607C/A), were correlated with development OLP or the severity of OLP. [17–20] However, these results were mixed, inconclusive, and even inconsistent.…”