Cao Jiali, Huang Yumei, Zhu Mengpei, Wang Ziwen, Jin Ze, Xiong Zhifan
Department of Gastroenterology, Liyuan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Front Nutr. 2024 May 27;11:1292834. doi: 10.3389/fnut.2024.1292834. eCollection 2024.
The causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator.
Summary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed.
As ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524-0.943; = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013-5.164; = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%.
This MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia.
在欧洲人群中，肌肉减少症与肝细胞癌（HCC）发病风险之间的因果关系，以及C反应蛋白（CRP）的潜在中介作用仍不明确。本研究采用双向两样本、两步孟德尔随机化（MR）分析来研究因果关系并确定中介因素。
从公开可用数据库中获取HCC、CRP以及与肌肉减少症相关特征（包括四肢瘦体重（ALM）、握力（HGS）和步速（WP））的汇总统计数据。我们进行了双向MR和方向性的Steiger检验，以检查是否存在反向因果关系。此外，采用两步MR分析来评估CRP在肌肉减少症与HCC因果关系中的中介作用。进行了异质性和水平多效性检验。
随着ALM增加，HCC发生风险降低[优势比（OR），95%置信区间（CI）：0.703，0.524 - 0.943；P = 0.019]。并且，基因预测的低HGS（OR，95%CI：2.287，1.013 - 5.164；P = 0.047）与HCC发病风险增加相关，不存在反向因果关系。然而，我们没有发现支持WP与HCC之间存在因果关系的证据。CRP被确定为ALM和低HGS对HCC因果效应的中介因素，相应的中介效应分别为9.1%和7.4%。
这项MR研究有效地证明，在欧洲人群中，较低的ALM和低HGS与HCC风险升高有关，且因果关系不是双向的。此外，CRP在这些关联中起中介作用。这些发现可能有助于降低肌肉减少症个体的HCC风险。
