Chang Yuan, Gao Guanzhuang, Feng Cuncheng
Department of Anorectal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Front Microbiol. 2024 Apr 2;15:1383530. doi: 10.3389/fmicb.2024.1383530. eCollection 2024.
Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental factors, and infections such as . Despite the known risk factors, the role of gut microbiota in the development of gastric cancer remains insufficiently explored. This study aims to elucidate the causal relationship between gut microbiota and gastric cancer using a two-sample Mendelian Randomization (MR) approach.
Utilizing genome-wide association study (GWAS) summary data from the MiBioGen consortium and gastric cancer datasets, we selected instrumental variables for MR analysis based on their association with specific microbiota. We employed several MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and others, to estimate the causal effects of gut microbiota diversity on the risk of developing gastric cancer.
Our analysis identified significant associations between certain gut microbiota and gastric cancer risk. Specifically, taxa such as (OR = 0.540, 95%CI: 0.354-0.823, = 0.004), (OR = 0.756, 95%CI: 0.613-0.932, = 0.009), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.863, 95%CI: 0.746-0.999, = 0.048) were found to have a protective effect against gastric cancer. Conversely, an increased risk of gastric cancer was associated with the abundance of (OR = 1.342, 95%CI: 1.071-1.681, = 0.011), (OR = 1.132, 95%CI: 1.012-1.267, = 0.030), and (OR = 1.207, 95%CI: 1.074-1.355, = 0.002). The findings were robust across various MR methods and were not driven by any single SNP, indicating a genuine causal relationship.
Our studies have shown that there is a causal relationship between intestinal flora and gastric cancer at the genetic level. , , , , , and as having a protective role against GC, while , , and were associated with an increased risk.
胃癌（GC）是全球第五大常见诊断癌症，其病因归因于遗传、饮食、环境因素以及感染等复杂的相互作用。尽管存在已知的风险因素，但肠道微生物群在胃癌发生中的作用仍未得到充分探索。本研究旨在使用两样本孟德尔随机化（MR）方法阐明肠道微生物群与胃癌之间的因果关系。
利用来自MiBioGen联盟的全基因组关联研究（GWAS）汇总数据和胃癌数据集，我们基于特定微生物群的关联选择用于MR分析的工具变量。我们采用了几种MR方法，包括逆方差加权（IVW）、MR-Egger、加权中位数等，以估计肠道微生物群多样性对患胃癌风险的因果效应。
我们的分析确定了某些肠道微生物群与胃癌风险之间的显著关联。具体而言，发现诸如（比值比[OR]=0.540，95%置信区间[CI]：0.354-0.823，P=0.004）、（OR=0.756，95%CI：0.613-0.932，P=0.009）、（OR=0.816，95%CI：0.666-1.000，P<0.05）、（OR=0.816，95%CI：0.666-1.000，P<0.05）、（OR=0.863，95%CI：0.746-0.999，P=0.048）等分类群对胃癌具有保护作用。相反，胃癌风险增加与（OR=1.342，95%CI：1.071-1.681，P=0.011）、（OR=1.132，95%CI：1.012-1.267，P=0.030）和（OR=1.207，95%CI：1.074-1.355，P=0.002）的丰度相关。这些发现通过各种MR方法都是稳健的，并且不是由任何单个单核苷酸多态性（SNP）驱动的，表明存在真正的因果关系。
我们的研究表明，在遗传水平上肠道菌群与胃癌之间存在因果关系。、、、、、对胃癌具有保护作用，而、和与风险增加相关。
