Yin Qiushi, Yang Qiuxi, Shi Wenjie, Kahlert Ulf D, Li Zhongyi, Lin Shibu, Song Qifeng, Fan Weiqiang, Wang Li, Zhu Yi, Huang Xiaolong
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 570100, China.
Molecular and Experimental Surgery, University Clinic for General-, Visceral-, Vascular- and Trans-Plantation Surgery, Medical Faculty University Hospital Magdeburg, Otto-von Guericke University, 39120 Magdeburg, Germany.
Cancers (Basel). 2023 May 26;15(11):2930. doi: 10.3390/cancers15112930.
Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers and liver cancer, the genetic association between these inflammatory traits and liver cancer remains elusive and merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using inflammatory traits as exposures and liver cancer as the outcome. The genetic summary data of both exposures and outcome were retrieved from previous genome-wide association studies (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, and weighted-mode methods, were employed to examine the genetic association between inflammatory traits and liver cancer. Nine extrahepatic immune-mediated diseases, seven circulating inflammatory biomarkers, and 187 inflammatory cytokines were analyzed in this study. The IVW method suggested that none of the nine immune-mediated diseases were associated with the risk of liver cancer, with odds ratios of 1.08 (95% CI 0.87-1.35) for asthma, 0.98 (95% CI 0.91-1.06) for rheumatoid arthritis, 1.01 (95% CI 0.96-1.07) for type 1 diabetes, 1.01 (95% CI 0.98-1.03) for psoriasis, 0.98 (95% CI 0.89-1.08) for Crohn's disease, 1.02 (95% CI 0.91-1.13) for ulcerative colitis, 0.91 (95% CI 0.74-1.11) for celiac disease, 0.93 (95% CI 0.84-1.05) for multiple sclerosis, and 1.05 (95% CI 0.97-1.13) for systemic lupus erythematosus. Similarly, no significant association was found between circulating inflammatory biomarkers and cytokines and liver cancer after correcting for multiple testing. The findings were consistent across all four MR methods used in this study. Our findings do not support a genetic association between extrahepatic inflammatory traits and liver cancer. However, larger-scale GWAS summary data and more genetic instruments are needed to confirm these findings.
肝癌与慢性炎症密切相关。虽然观察性研究报告了肝外免疫介导疾病和全身炎症生物标志物与肝癌之间存在正相关，但这些炎症特征与肝癌之间的遗传关联仍不明确，值得进一步研究。我们进行了一项两样本孟德尔随机化（MR）分析，将炎症特征作为暴露因素，肝癌作为结局。暴露因素和结局的遗传汇总数据均取自先前的全基因组关联研究（GWAS）。我们采用了四种MR方法，包括逆方差加权（IVW）、MR-Egger回归、加权中位数和加权模式方法，来检验炎症特征与肝癌之间的遗传关联。本研究分析了九种肝外免疫介导疾病、七种循环炎症生物标志物和187种炎症细胞因子。IVW方法表明，九种免疫介导疾病中没有一种与肝癌风险相关，哮喘的比值比为1.08（95%CI 0.87-1.35），类风湿性关节炎为0.98（95%CI 0.91-1.06），1型糖尿病为1.01（95%CI 0.96-1.07），银屑病为1.01（95%CI 0.98-1.03），克罗恩病为0.98（95%CI 0.89-1.08），溃疡性结肠炎为1.02（95%CI 0.91-1.13），乳糜泻为0.91（95%CI 0.74-1.11），多发性硬化症为0.93（95%CI 0.84-1.05），系统性红斑狼疮为1.05（95%CI 0.97-1.13）。同样，在进行多重检验校正后，未发现循环炎症生物标志物和细胞因子与肝癌之间存在显著关联。本研究使用的所有四种MR方法的结果均一致。我们的研究结果不支持肝外炎症特征与肝癌之间存在遗传关联。然而，需要更大规模的GWAS汇总数据和更多的遗传工具来证实这些发现。
