The role of TLR2, TLR4 and CD14 genetic polymorphisms in gastric carcinogenesis: a case-control study and meta-analysis.
The role of TLR2, TLR4 and CD14 genetic polymorphisms in gastric carcinogenesis: a case-control study and meta-analysis.
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DOI：
10.1371/journal.pone.0060327
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mitchell HM
中科院分区：
文献类型：
--
作者：
Castaño-Rodríguez N;Kaakoush NO;Goh KL;Fock KM;Mitchell HM
除了幽门螺杆菌感染，宿主遗传因素也是胃癌（GC）的原因。对H.已知幽门螺杆菌涉及Toll样受体（TLR），其随后导致NF-κB的活化。因此，本研究的总体目的是通过荟萃分析首次估计TLR 2、TLR 4和CD 14多态性对GC发展的合并效应大小。采用PCR、RT-PCR和质谱技术对284例中国汉族人（70例非贲门胃癌患者和214例功能性消化不良对照）进行了TLR 2 - 196 ~-174 del、CD 14 - 260 C/T和TLR 4 rs 11536889基因分型。检索了截至2012年6月的TLR 2、TLR 4和CD 14多态性与GC的病例对照研究。通过随机效应模型获得合并优势比和95%置信区间。在我们的中国少数民族病例对照研究中，TLR 4 rs 11536889 C等位基因增加GC的风险（OR：1.89，95%CI：1.23-2.92），而CD 14 - 260 T等位基因具有保护性（OR：0.62，95%CI：0.42-0.91）。TLR 2 - 196 ~-174仅在H.幽门螺杆菌感染者（OR：3.10，95%CI：1.27-7.60）。在荟萃分析中，TLR 4 Asp 299 Gly在一般分析中显示了临界结果（合并OR：1.58，95%CI：0.98-2.60），然而，按种族分层分析显示，突变等位基因是西方人群中GC的明确风险因素（合并OR：1.87，95%CI：1.31-2.65）。在日本人中，TLR 2 - 196至-174缺失等位基因与GC之间存在潜在关联（合并OR：1.18，95%CI：0.96-1.45）。TLR 4 Thr 399 Ile没有提供显著的结果。 TLR 4 rs 11536889和CD 14 - 260 C/T与中国人非贲门癌相关基于我们的荟萃分析，TLR信号通路参与胃癌的发生，TLR 4 Asp 299 Gly和TLR 2 - 196至-174del以种族特异性方式显示与GC的关联。
In addition to Helicobacter pylori infection, host genetic factors contribute to gastric cancer (GC). Recognition of H. pylori is known to involve Toll-like receptors (TLR), which subsequently leads to activation of NF-κB. Thus, the overall aim of this study was to estimate for the first time the pooled effect size of polymorphisms in TLR2, TLR4 and CD14 on GC development through a meta-analysis. A case-control study comprising 284 ethnic Chinese individuals (70 non-cardia GC cases and 214 functional dyspepsia controls) was conducted for the genotyping of TLR2 -196 to -174del, CD14 -260 C/T and TLR4 rs11536889 using PCR, RT-PCR and mass spectrometry. Case-control studies of TLR2, TLR4 and CD14 polymorphisms and GC were searched up to June 2012. Pooled odds ratios and 95% confidence intervals were obtained by means of the random effects model. In our ethnic Chinese case-control study, the TLR4 rs11536889 C allele increased the risk of GC (OR: 1.89, 95%CI: 1.23–2.92) while the CD14 -260 T allele was protective (OR: 0.62, 95%CI: 0.42–0.91). TLR2 -196 to -174 increased the risk of GC only in H. pylori-infected individuals (OR: 3.10, 95%CI: 1.27–7.60). In the meta-analysis, TLR4 Asp299Gly showed borderline results in the general analysis (pooled OR: 1.58, 95%CI: 0.98–2.60), nevertheless, stratified analysis by ethnicity showed that the mutant allele was a definitive risk factor for GC in Western populations (pooled OR: 1.87, 95%CI: 1.31–2.65). There was a potential association between the TLR2 -196 to -174 deletion allele and GC in Japanese (pooled OR: 1.18, 95%CI: 0.96–1.45). TLR4 Thr399Ile did not provide significant results. TLR4 rs11536889 and CD14 -260 C/T are associated with non-cardia GC in Chinese. Based on our meta-analysis, the TLR signalling pathway is involved in gastric carcinogenesis, TLR4 Asp299Gly and TLR2 -196 to -174del showing associations with GC in an ethnic-specific manner.
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2.2
作者：
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影响因子：
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Hishida, Asahi;Matsuo, Keitaro;Hamajima, Nobuyuki
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Hamajima, Nobuyuki
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Garza-Gonzalez E;Bosques-Padilla FJ;Mendoza-Ibarra SI;Flores-Gutierrez JP;Maldonado-Garza HJ;Perez-Perez GI
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作者：
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ERNST, PB