School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
School of Humanities, Social Sciences and Law, University of Dundee, Dundee, Scotland, UK.
BMC Cancer. 2023 Oct 24;23(1):1027. doi: 10.1186/s12885-023-11509-7.
Gastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies.
This study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.
Eight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90-1.67, I = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I = 0%, non-Asian: OR = 1.25, 95%CI = 0.38-4.09, I = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74-2.64, I = 85%; Asian: OR: 1.41, 95% CI = 1.07-1.86, I = 0%, non-Asian: OR = 1.18, 95% CI = 0.12-11.76, I = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76-2.86, I = 82%; Asian: OR = 1.54, 95% CI = 1.13-2.1, I = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89-1.71, I = 84%; Asian: OR = 1.22, 95% CI = 1.05-1.41, I = 0%; non-Asian: OR = 1.24, 95% CI = 0.34-4.59, I = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.
The findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.
胃癌具有复杂的病因，包括遗传因素。已有一些关于 Toll 样受体（TLR）9（-1237 T/C、-1486 T/C）多态性与胃癌风险的个体病例对照研究，其结果存在差异。因此，我们进行了一项荟萃分析，以综合评估 TLR 9（-1237 T/C、-1486 T/C）多态性与胃癌风险之间的关联，纳入了来自合格研究的数据。
本研究遵循 PRISMA 2020 清单。在健康相关数据库中搜索研究。使用纽卡斯尔-渥太华量表标准评估研究的方法学质量。使用五种遗传模型，计算每个多态性与胃癌风险之间关联的汇总优势比（OR）及其 95%置信区间（CI）。通过分层按种族进行分析。为了分析的稳健性，进行了一项剔除一个研究的荟萃分析。
在六个国家进行了八项病例对照研究，共纳入 3644 名参与者（1914 例病例，1730 例对照）。其中一半的研究在中国进行。在 NOS 方法学质量评估中，仅有三项研究获得了高质量评分（即评分≥7）。在六项研究中评估了 TLR 9（-1486 T/C）多态性与胃癌风险之间的关联，其中四项为亚洲人群，两项为非亚洲人群。在显性模型下，仅在亚洲人群中显示出胃癌风险略有且显著增加（总体：OR=1.22，95%CI=0.90-1.67，I=56%；亚洲：OR=1.24，95%CI=1.00-1.54，I=0%，非亚洲：OR=1.25，95%CI=0.38-4.09，I=89%）。在不存在异质性的隐性模型下，仅亚洲人群患胃癌的风险显著增加（总体：OR=1.4，95%CI=0.74-2.64，I=85%；亚洲：OR=1.41，95%CI=1.07-1.86，I=0%，非亚洲：OR=1.18，95%CI=0.12-11.76，I=97%）。在杂合模型下，与胃癌风险之间无显著关联，无论任何种族亚组。在不存在异质性的纯合模型下，仅亚洲人群患胃癌的风险显著增加（总体：OR=1.47，95%CI=0.76-2.86，I=82%；亚洲：OR=1.54，95%CI=1.13-2.1，I=0%，非亚洲：OR=1.19，95%CI=0.1-14.33，I=96%）。在等位基因模型下，仅在亚洲人群中观察到胃癌风险显著增加（总体：OR=1.23，95%CI=0.89-1.71，I=84%；亚洲：OR=1.22，95%CI=1.05-1.41，I=0%，非亚洲：OR=1.24，95%CI=0.34-4.59，I=97%）。四项研究探讨了 TLR 9（-1237 T/C）多态性与胃癌风险之间的关系。在任何五种遗传模型下，TLR 9（-1237 T/C）与胃癌的发生之间均无关联，无论在总体人群还是任何种族亚组中。敏感性分析表明，该效应不稳定。由于研究数量较少，参与者数量较少，我们解决了得出结论的能力不足的问题。
研究结果表明，TLR9（-1486 T/C）可能在特定于亚洲人群的胃癌风险中起作用。为了证实这两种多态性（TLR9-1237 T/C、-1486 T/C）与胃癌风险之间的关联，建议未来在多民族群体中进行设计良好、样本量足够的病例对照研究。
