Gao Xing, Gao Hao, Wang Song, Tang Futian, Zhao Yang, Li Yumin
Gansu Province Key Laboratory of Environmental Oncology, The Second Clinical Medical College of Lanzhou University, Lanzhou, 730000, Gansu, China.
School of Life Sciences of Lanzhou University, Lanzhou, 730000, Gansu Province, China.
BMC Gastroenterol. 2025 Aug 26;25(1):619. doi: 10.1186/s12876-025-04199-x.
Over the past few decades, the global incidence of cholangiocarcinoma has risen overall. In particular, the incidence of intrahepatic cholangiocarcinoma increased by 109% over a ten-year period, rising from 0.67 per 100,000 in 2007 to 1.40 per 100,000 in 2016. Epidemiological studies have suggested that cholecystitis may increase the risk of hepatobiliary cancers. However, whether this association indicates an independent causal relationship remains unclear. Given that observational studies are prone to residual confounding and bias, limiting the strength of causal inference. Our study aimed to evaluate whether cholecystitis is an independent risk factor for cholangiocarcinoma.
Instrumental variables were identified as independent single nucleotide polymorphisms highly associated with cholecystitis (n = 25). The entire dataset from the Integrative Epidemiology Unit (IEU) publicly available genome-wide association studies (GWAS) was utilized to obtain cholangiocarcinoma outcome data (n = 25). In this study, five MR statistical techniques (Inverse Variance Weighted, MR Egger, Weighted Median, Simple Mode, and Weighted mode) were used. The MR Egger intercept test, leave-one-out analysis, and the funnel plot were all utilized in sensitivity analyses.
Results of the Inverse Variance Weighted (IVW) method genetically predicted cholecystitis was associated with higher risk of cholangiocarcinoma, with an odds ratio of 2.915 (95% CI = 1.122-7.575, P = 0.038). Weighted Median Method also demonstrated consistent direction of effect (P = 0.016). However, MR-Egger, Simple Mode, and Weighted Mode all showed no statistical significance (P > 0.05). Both funnel plots and MR Egger intercepts indicated the absence of any directional pleiotropic effects between cholecystitis and cholangiocarcinoma.
We found evidence supporting a causal effect between cholecystitis and cholangiocarcinoma, indicating an increased likelihood of cholangiocarcinoma in patients with cholecystitis through MR analysis.These findings may help inform clinical strategies for the management of cholecystitis, with the aim of potentially reducing the risk of cholangiocarcinoma.
在过去几十年中，全球胆管癌的发病率总体呈上升趋势。特别是，肝内胆管癌的发病率在十年间增长了109%，从2007年的每10万人0.67例升至2016年的每10万人1.40例。流行病学研究表明，胆囊炎可能会增加肝胆癌的风险。然而，这种关联是否表明存在独立的因果关系仍不清楚。鉴于观察性研究容易出现残余混杂和偏差，限制了因果推断的力度。我们的研究旨在评估胆囊炎是否是胆管癌的独立危险因素。
将工具变量确定为与胆囊炎高度相关的独立单核苷酸多态性（n = 25）。利用综合流行病学单位（IEU）公开的全基因组关联研究（GWAS）的整个数据集来获取胆管癌结局数据（n = 25）。在本研究中，使用了五种孟德尔随机化（MR）统计技术（逆方差加权法、MR-Egger法、加权中位数法、简单模式法和加权模式法）。敏感性分析中采用了MR-Egger截距检验、留一法分析和漏斗图。
逆方差加权（IVW）法的结果显示，遗传预测的胆囊炎与胆管癌风险较高相关，比值比为2.915（95%置信区间=1.122-7.575，P = 0.038）。加权中位数法也显示出一致的效应方向（P = 0.016）。然而，MR-Egger法、简单模式法和加权模式法均未显示出统计学意义（P>0.05）。漏斗图和MR-Egger截距均表明胆囊炎和胆管癌之间不存在任何方向性多效性效应。
我们发现有证据支持胆囊炎与胆管癌之间存在因果效应，通过MR分析表明胆囊炎患者患胆管癌的可能性增加。这些发现可能有助于为胆囊炎的临床管理策略提供信息，以期潜在地降低胆管癌风险。
