Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, USA.
Gene. 2014 Mar 1;537(1):46-50. doi: 10.1016/j.gene.2013.12.030. Epub 2013 Dec 21.
Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene-environmental interactions on the risk of GC in Northeastern China.
We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.
Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR=0.33, 95% CI 0.18-0.60, P<0.001 and adjusted OR=0.37, 95% CI 0.21-0.67, P=0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.
Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.
Toll 样受体 4(TLR4)是胃上皮细胞信号转导中重要的脂多糖(LPS)受体,在胃癌(GC)的发生和发展中起关键作用。我们研究了 TLR4 基因多态性及其与环境因素的相互作用对中国东北地区 GC 发病风险的影响。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对 217 例 GC 患者和 294 例无癌对照者的 TLR4 两个单核苷酸多态性(SNPs)(rs10116253 和 rs1927911)进行基因分型。采用非条件 logistic 回归模型估计比值比(OR)和 95%置信区间(CI)。
与 rs10116253 的 TT 基因型和 rs1927911 的 CC 基因型相比,携带 rs10116253 的 CC 基因型和 rs1927911 的 TT 基因型的个体患 GC 的风险显著降低(调整后的 OR=0.33,95%CI 0.18-0.60,P<0.001 和调整后的 OR=0.37,95%CI 0.21-0.67,P=0.001)。此外,在 GC 易感性方面,这些 SNP 效应与一些已知的环境因素的效应呈累加关系,且它们之间没有相互作用。
我们的数据表明,TLR4 基因多态性可能与中国人群 GC 发病风险降低有关。这些 SNP 及其与环境因素的综合作用可能与 GC 发病风险有关。