孟德尔随机化
医学
混淆
全基因组关联研究
内科学
肝癌
病例对照研究
肿瘤科
癌症
生物
遗传学
单核苷酸多态性
基因型
基因
遗传变异
作者
Jun Ma,Jialiang Li,Chen Jin,Jinhuan Yang,Chongming Zheng,Kaiwen Chen,Yitong Xie,Yi Yang,Zhiyuan Bo,Jingxian Wang,Qing Su,Juejin Wang,Gang Chen,Yi Wang
摘要
Abstract Background and Aims Observational epidemiology studies suggested a relationship between the gut microbiome and primary liver cancer. However, the causal relationship remains unclear because of confounding factors and reverse causality. We aimed to explore the causal role of the gut microbiome in the development of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods Mendelian randomization (MR) study was conducted using summary statistics from genome‐wide association studies (GWAS) of the gut microbiome and liver cancer, and sequencing data from a case–control study validated the findings. A 5‐cohort GWAS study in Germany ( N = 8956) served as exposure, whilst the UK biobank GWAS study ( N = 456 348) served as an outcome. The case–control study was conducted at the First Affiliated Hospital of Wenzhou Medical University from December 2018 to October 2020 and included 184 HCC patients, 63 ICC patients and 40 healthy controls. Results A total of 57 features were available for MR analysis, and protective causal associations were identified for Family_Ruminococcaceae (OR = 0.46 [95% CI, 0.26–0.82]; p = .009) and Genus_Porphyromonadaceae (OR = 0.59 [95% CI, 0.42–0.83]; p = .003) with HCC, and for Family_Porphyromonadaceae (OR = 0.36 [95% CI, 0.14–0.94]; p = .036) and Genus_Bacteroidetes (OR = 0.55 [95% CI, 0.34–0.90]; p = .017) with ICC respectively. The case–control study results showed that the healthy controls had a higher relative abundance of Family_Ruminococcaceae ( p = .00033), Family_Porphyromonadaceae ( p = .0055) and Genus_Bacteroidetes ( p = .021) than the liver cancer patients. Conclusions This study demonstrates that Ruminococcaceae , Porphyromonadaceae and Bacteroidetes are related to a reduced risk of liver cancer (HCC or ICC), suggesting potential significance for the prevention and control of liver cancer.
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