Tao Xuewen, Mao Shuai, Wang Jincheng, Li Guoqiang, Sun Beicheng
School of Medicine, Southeast University, Nanjing 210009, China.
Anhui Medical University, Hefei 230022, China.
Biomedicines. 2024 Jul 11;12(7):1537. doi: 10.3390/biomedicines12071537.
Diverse clinical observations and basic studies have been conducted to explore the implications of analgesic medications in liver diseases. However, the direct causal relationship between prescription analgesic use (PAU) and the risk of liver cancer and precancerosis remains unclear. Thus, we aimed to reveal the conceivable causal effect of PAU on liver cancer and precancerosis, with immune cells as mediating factors. Two-sample Mendelian randomization (MR) analyses were performed to ascertain the causality of PAU on liver cancer and precancerosis. Sensitivity analysis approaches were employed to assess the heterogeneity and pleiotropy of results. Our findings revealed a causal correlation between different PAUs and the risk of liver cancer and alcoholic liver disease (ALD). Specifically, salicylic acid derivatives (SADs) and anilide medications were found to have a protective effect on liver cancer. And non-steroidal anti-inflammatory drugs (NSAIDs) and anilide medications showed a causal impact on ALD. Finally, mediation analyses found that anilide medications influence liver cancer through different immune cell phenotypes. Our research provides new genetic evidence for the causal impact of PAU on liver cancer and precancerosis, with the mediating role of immune cells demonstrated, offering a valuable foundation for researching analgesic medications in liver cancer and precancerosis treatment.
人们已经进行了各种临床观察和基础研究，以探索止痛药物在肝脏疾病中的影响。然而，处方止痛药物使用（PAU）与肝癌及癌前病变风险之间的直接因果关系仍不明确。因此，我们旨在揭示以免疫细胞为中介因素时，PAU对肝癌和癌前病变可能存在的因果效应。我们进行了两样本孟德尔随机化（MR）分析，以确定PAU对肝癌和癌前病变的因果关系。采用敏感性分析方法评估结果的异质性和多效性。我们的研究结果揭示了不同PAU与肝癌和酒精性肝病（ALD）风险之间的因果关联。具体而言，发现水杨酸衍生物（SADs）和酰苯胺类药物对肝癌具有保护作用。并且非甾体抗炎药（NSAIDs）和酰苯胺类药物对ALD有因果影响。最后，中介分析发现酰苯胺类药物通过不同的免疫细胞表型影响肝癌。我们的研究为PAU对肝癌和癌前病变的因果影响提供了新的遗传学证据，证明了免疫细胞的中介作用，为研究止痛药物在肝癌和癌前病变治疗中的应用提供了有价值的基础。
