Zeljic K, Supic G, Jovic N, Kozomara R, Brankovic-Magic M, Obrenovic M, Magic Z
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia; Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Oral Dis. 2014 May;20(4):416-24. doi: 10.1111/odi.12144. Epub 2013 Jun 24.
The aim of this study is to investigate association between polymorphisms in TLR2, TLR3, TLR4 and CD14 genes or their haplotypes with oral squamous cell carcinomas (OSCC) risk and survival.
The study was conducted on 93 OSCC patients and 104 cancer-free controls. Polymorphisms were genotyped by real-time PCR or PCR-RFLP method.
Significant increase in oral cancer risk was observed in individuals with mutated genotype of TLR3 rs3775291 polymorphism (OR = 1.096, P = 0.036) compared to wild-type. The heterozygous and mutated genotype of TLR3 rs5743312 polymorphism had worse survival in group of patients with stage III tumours (P = 0.043). Multivariate Cox regression analysis revealed that TLR3 rs5743312 polymorphism could be considered as prognostic marker in advanced III stage OSCC (HR = 2.456, P = 0.007), but not independently of nodal status. TLR3 rs3775291 and rs5743312 polymorphisms were in strong linkage disequilibrium. Haplotype TG was associated with worse prognosis in OSCC patients in comparison with common CG haplotype (HR = 1.717, P = 0.042). Interaction among polymorphisms in TLR2, TLR3 and CD14 genes was observed (P = 0.010).
TLR3 rs5743312 polymorphism could be considered as potential predictor of worse overall survival in advanced oral cancer, but not independently of nodal status. Haplotypes in TLR3 gene might be associated with poor prognosis in OSCC patients.
本研究旨在调查Toll样受体2（TLR2）、Toll样受体3（TLR3）、Toll样受体4（TLR4）和CD14基因的多态性或其单倍型与口腔鳞状细胞癌（OSCC）风险及生存之间的关联。
对93例OSCC患者和104例无癌对照者进行研究。采用实时聚合酶链反应（PCR）或聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对多态性进行基因分型。
与野生型相比，TLR3 rs3775291多态性突变基因型个体的口腔癌风险显著增加（比值比[OR]=1.096，P=0.036）。TLR3 rs5743312多态性的杂合子和突变基因型在Ⅲ期肿瘤患者组中生存较差（P=0.043）。多因素Cox回归分析显示，TLR3 rs5743312多态性可被视为晚期Ⅲ期OSCC的预后标志物（风险比[HR]=2.456，P=0.007），但不独立于淋巴结状态。TLR3 rs3775291和rs5743312多态性处于强连锁不平衡状态。与常见的CG单倍型相比，单倍型TG与OSCC患者的预后较差相关（HR=1.717，P=0.042）。观察到TLR2、TLR3和CD14基因多态性之间存在相互作用（P=0.010）。
TLR3 rs5743312多态性可被视为晚期口腔癌总体生存较差的潜在预测指标，但不独立于淋巴结状态。TLR3基因的单倍型可能与OSCC患者的预后不良相关。
