Hsu Han-Jen, Yang Yi-Hsin, Shieh Tien-Yu, Chen Chung-Ho, Kao Yu-Hsun, Yang Chia-Fu, Ko Edward Cheng-Chuan
Department of Oral and Maxillofacial Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
Kaohsiung J Med Sci. 2014 Nov;30(11):551-8. doi: 10.1016/j.kjms.2014.09.003. Epub 2014 Oct 27.
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.
口腔鳞状细胞癌之前可能会出现一些具有恶变潜能的良性口腔病变，包括白斑、红斑、口腔扁平苔藓和口腔黏膜下纤维化。组织病理学检查可见不同程度的炎性细胞浸润。炎性细胞因子可能在口腔癌前病变（OPCLs）的发生发展中起致病作用。已知细胞因子编码基因的遗传多态性易导致恶性疾病。我们推测，OPCLs的风险可能与干扰素（IFN）-γ、转化生长因子（TGF）-β1、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-10的细胞因子基因多态性有关。在本研究中，对42例OPCL患者和128例对照者分析了5种不同细胞因子基因中的8种多态性[IFN-γ（+874 T/A）、TGF-β1（密码子10 T/C和25 G/C）、TNF-α（-308 G/A）、IL-6（-174 G/C）和IL-10（-1082 A/G、-819 T/C和-592 A/C）]。使用商业引物通过聚合酶链反应序列特异性引物技术确定细胞因子基因分型。采用卡方（χ(2)）检验分析病例组和对照组之间等位基因和基因型数据差异的显著性。双侧p < 0.05被认为具有统计学意义。构建了一系列经年龄、性别、嚼槟榔、饮酒和吸烟校正的多因素逻辑回归模型，以评估多态性纯合或杂合变异基因型的贡献。TNF-α（-308）多态性与OPCLs显著相关。OPCL患者与对照组之间AA、GA和GG基因型的分布存在显著差异（p = 0.0004）。AA或GA基因型的患者发生OPCLs的风险增加3.63倍。TGF-β1（密码子10和25）多态性也与OPCLs显著相关（p < 0.001）。IL-6多态性与OPCLs显著相关。OPCL患者与对照组之间CC、GC和GG基因型的分布存在显著差异（p < 0.001）。CC或GC基因型的患者发生OPCLs的风险分别增加35倍或20.59倍。不同对照组个体与OPCL患者之间IL-10和IFN-γ基因型的分布无显著差异。IL-6、TGF-β1和TNF-α基因多态性可能与OPCLs的发生显著相关。
