Li Ze, Gao Hui, Liu Yang, Wu Hongjiao, Li Weiyuan, Xing Yunce, Zhang Zhi, Zhang Xuemei
School of Public Health, North China University of Science and Technology, Tangshan 063210, China; College of Life Science, North China University of Science and Technology, Tangshan 063210, China.
College of Life Science, North China University of Science and Technology, Tangshan 063210, China.
Gene. 2021 Jan 30;767:145181. doi: 10.1016/j.gene.2020.145181. Epub 2020 Sep 30.
Gastric cancer (GC) is one of the most common cancers diagnosed in China. It has been suggested that the genetic polymorphisms of Toll-like receptors (TLRs) might be in close relation to tumorigenesis and development of gastric cancer. In this study, we performed a case-control study to investigate the genetic polymorphisms of TLR3, 4, 5, 7 with the genetic susceptibility of gastric cancer. TLRs gene polymorphisms in 471 gastric cancer (GC) patients and 471 healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis or TaqMan assays. Odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the association of TLR4 variants with the GC risk via unconditional logistic regression. Our results suggested that variant genotypes of TLR4 rs7869402 (OR = 0.61, 95%CI = 0.40-0.92, P = 0.02) and TLR4 rs7873784 (OR = 0.17, 95%CI = 0.09-0.33, P < 0.01) gene polymorphisms reduced the risk of GC. Stratified analysis showed that rs7869402 T-containing genotype significantly decreased the susceptibility of GC among females (OR = 0.38, 95%CI = 0.16-0.91, P = 0.03), older subjects (OR = 0.48, 95%CI = 0.26-0.87, P = 0.02), non-smokers (OR = 0.41, 95%CI = 0.23-0.71, P < 0.01) and non-drinkers (OR = 0.58, 95%CI = 0.30-0.78, P < 0.01). In case of rs7873784 polymorphism, C-containing genotype reduced the risk of GC among males (OR = 0.08, 95%CI = 0.03-0.21, P < 0.01), but not among females (OR = 0.53, 95%CI = 0.22-1.27, P = 0.15). As to the other four SNPs (TLR3 rs5743303, TLR4 rs1927914, TLR5 rs1640816 and TLR7 rs3853839), no significant correlations were found to be related to the risk of gastric carcinoma. Our research demonstrated the significance of TLRs polymorphisms in decreasing the risk of GC.
胃癌（GC）是中国诊断出的最常见癌症之一。有人提出，Toll样受体（TLR）的基因多态性可能与胃癌的发生和发展密切相关。在本研究中，我们进行了一项病例对照研究，以调查TLR3、4、5、7的基因多态性与胃癌遗传易感性的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析或TaqMan分析，对471例胃癌（GC）患者和471例健康对照者的TLRs基因多态性进行了分析。通过无条件逻辑回归，使用比值比（OR）及其95%置信区间（95%CI）来评估TLR4变体与GC风险的关联。我们的结果表明，TLR4 rs7869402（OR = 0.61，95%CI = 0.40-0.92，P = 0.02）和TLR4 rs7873784（OR = 0.17，95%CI = 0.09-0.33，P < 0.01）基因多态性的变异基因型降低了GC风险。分层分析表明，含rs7869402 T的基因型显著降低了女性（OR = 0.38，95%CI = 0.16-0.91，P = 0.03）、老年受试者（OR = 0.48，95%CI = 0.26-0.87，P = 0.02）、非吸烟者（OR = 0.41，95%CI = 0.23-0.71，P < 0.01）和非饮酒者（OR = 0.58，95%CI = 0.30-0.78，P < 0.01）患GC的易感性。就rs7873784多态性而言，含C的基因型降低了男性患GC的风险（OR = 0.08，95%CI = 0.03-0.21，P < 0.01），但在女性中未降低（OR = 0.53，95%CI = 0.22-1.27，P = 0.15）。至于其他四个单核苷酸多态性（TLR3 rs5743303、TLR4 rs1927914、TLR5 rs1640816和TLR7 rs3853839），未发现与胃癌风险有显著相关性。我们的研究证明了TLRs多态性在降低GC风险方面的重要性。
