TLR2 和 TLR4 基因的多态性与巴西人群胃癌的风险相关。
Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population.
机构信息
Department of Biology, UNESP- São Paulo State University, São José do Rio Preto Campus, 15054-000 SP, Brazil.
出版信息
World J Gastroenterol. 2012 Mar 21;18(11):1235-42. doi: 10.3748/wjg.v18.i11.1235.
AIM
To investigate toll-like receptor 2 (TLR2) -196 to -174 del, and TLR4 (+896A/G rs4986790 and +1196C/T rs4986791) polymorphisms at risk of chronic gastritis and gastric cancer in a Brazilian population and association of gastric lesions with risk factors such as smoking, alcohol intake and Helicobacter pylori infection.
METHODS
In this case-control study, polymorphism at TLR2 -196 to -174 del was investigated by using the allele-specific polymerase chain reaction (PCR) method, while the PCR-restriction fragment length polymorphism technique was carried out to identify the TLR4 (rs4986790 and rs4986791) genotypes in 607 Brazilian individuals (208 with chronic gastritis-CG, 174 with gastric cancer-GC and 225 controls -C).
RESULTS
The single nucleotide polymorphisms TLR4+1196C/T was not associated with risk of chronic gastritis or gastric cancer and the homozygous genotypes TLR4+896GG and TLR4+1196TT were absent in the studied population. However, the frequency of TLR2 -196 to -174 ins/del + del/del and TLR4+896AG genotypes was significantly higher (P < 0.01 and P = 0.01, respectively) in the cancer group (33.4% and 11.5%, respectively) than in the control group (16.9% and 4.5%, respectively). It was also observed that the G-C haplotype of the TLR4+896A/G+1196C/T (P = 0.02) and the combination of variant alleles of the TLR2/TLR4+896G (P = 0.02) are associated with susceptibility to gastric cancer. In addition, the multiple logistic regression showed that male gender [odds ratio (OR) = 2.70; 95% CI: 1.66-4.41; P < 0.01], alcohol intake (OR = 2.93; 95% CI: 1.76-4.87; P < 0.01), TLR2 -196 to -174 del (OR = 2.64; 95% CI: 1.56-4.44; P < 0.01) and TLR4+896G (OR = 3.19; 95% CI: 1.34- 7.61; P < 0.01) polymorphisms were associated with a higher susceptibility to developing this neoplasm.
CONCLUSION
Our data indicate that TLR2 -196 to -174 del and TLR4+896G may increase the risk of gastric cancer in a Brazilian population.
目的
探讨 Toll 样受体 2（TLR2）-196 到-174 缺失、TLR4（+896A/G rs4986790 和+1196C/T rs4986791）多态性与巴西人群慢性胃炎和胃癌的发病风险，并分析胃病变与吸烟、饮酒和幽门螺杆菌感染等危险因素的关系。
方法
采用等位基因特异性聚合酶链反应（PCR）方法检测 TLR2-196 到-174 缺失的多态性，采用 PCR-限制性片段长度多态性技术检测 TLR4（rs4986790 和 rs4986791）基因型。在 607 名巴西个体（208 名慢性胃炎-CG、174 名胃癌-GC 和 225 名对照-C）中进行了研究。
结果
TLR4+1196C/T 单核苷酸多态性与慢性胃炎或胃癌的发病风险无关，且在所研究人群中未发现 TLR4+896GG 和 TLR4+1196TT 纯合基因型。然而，TLR2-196 到-174 ins/del+del/del 和 TLR4+896AG 基因型的频率在癌症组中明显更高（P<0.01 和 P=0.01），分别为 33.4%和 11.5%，而在对照组中分别为 16.9%和 4.5%。还观察到 TLR4+896A/G+1196C/T 的 G-C 单倍型（P=0.02）和 TLR2/TLR4+896G 变异等位基因的组合（P=0.02）与胃癌易感性相关。此外，多因素逻辑回归显示，男性（比值比[OR]=2.70；95%置信区间[CI]：1.66-4.41；P<0.01）、饮酒（OR=2.93；95%CI：1.76-4.87；P<0.01）、TLR2-196 到-174 缺失（OR=2.64；95%CI：1.56-4.44；P<0.01）和 TLR4+896G（OR=3.19；95%CI：1.34-7.61；P<0.01）多态性与发展这种肿瘤的更高易感性相关。
结论
我们的数据表明，TLR2-196 到-174 缺失和 TLR4+896G 可能会增加巴西人群患胃癌的风险。
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