Bai Ye, Zhang Min, Chen Lin, Zhou Peiwen, Zhou Bai, Wang Ruobing, Li Rixin, Si Junzhuo, Zhou Shuai, Jiang Yanfang
Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Clinical and Public Health Research Center, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
J Adv Res. 2025 Mar 8. doi: 10.1016/j.jare.2025.03.010.
Observational studies have shown that gallstone disease (GSD), cholecystitis, cholangitis, polyp of gallbladder, viral hepatitis, pancreatitis and gastrointestinal (GI) traits such as H. pylori infection, inflammatory bowel disease, and digestive ulcer are associated with the risk of biliary tract cancer (BTC). However, no study has explored their causal associations.
To gain a more comprehensive understanding of the causal relationships between GI traits, inflammatory diseases of the digestive system, gallstones, and the development of BTC, further investigation into a comprehensive causal network is warranted.
Based on findings of our Meta-analysis, the present study proposed to investigate the causal role of GSD (26,122 recorded cases) together with 15 GIs and common digestive system inflammatory diseases (sample size from 14,890 to 602,604) in the risk of incident BTC (832 cases and 475,259 controls), using a network Mendelian randomization. Independent associations were further discovered.
We found significant positive associations between GSD (OR = 1.26, 95 %CI: 1.05-1.51), cholecystitis (OR = 1.43, 95 %CI: 1.20-1.69), gallbladder polyps (OR = 1.11, 95 %CI: 1.00-1.24), primary sclerosing cholangitis (PSC, OR = 1.07, 95 %CI: 1.00-1.13), ulcerative colitis (UC, OR = 1.07, 95 %CI: 1.00-1.14) and the risk of BTC. The association of GSD with BTC was attenuated after adjusting for cholecystitis and gallbladder polyps (OR = 1.45, 95 %CI: 0.60-3.52), while the association of UC remained significant, without the mediation of biliary tract diseases (OR = 1.12, 95 %CI: 1.03-1.22). Beyond that, we verified that the causal associations between primary biliary cholangitis, viral hepatitis, chronic pancreatitis, gastritis, gastric ulcer, Crohn's disease, irritable bowel syndrome, peptic ulcer disease, gastroesophageal reflux disease, appendicitis, and an increased risk of BTC were not significant.
Our results implicate the effect of GSD on incident BTC to interact with cholecystitis and polyp of gallbladder, while UC as an independent risk factor for BTC. Clinical studies are needed to determine our findings.
观察性研究表明，胆结石病（GSD）、胆囊炎、胆管炎、胆囊息肉、病毒性肝炎、胰腺炎以及胃肠道（GI）特征，如幽门螺杆菌感染、炎症性肠病和消化性溃疡，都与胆道癌（BTC）的风险相关。然而，尚无研究探讨它们之间的因果关系。
为了更全面地了解胃肠道特征、消化系统炎症性疾病、胆结石与BTC发生之间的因果关系，有必要进一步研究一个综合的因果网络。
基于我们的荟萃分析结果，本研究建议使用网络孟德尔随机化方法，研究GSD（记录病例26,122例）以及15种胃肠道疾病和常见消化系统炎症性疾病（样本量从14,890到602,604）在新发BTC风险（832例病例和475,259例对照）中的因果作用。进一步发现独立关联。
我们发现GSD（比值比[OR]=1.26，95%置信区间[CI]：1.05 - 1.51）、胆囊炎（OR = 1.43，95%CI：1.20 - 1.69）、胆囊息肉（OR = 1.11，95%CI：1.00 - 1.24）、原发性硬化性胆管炎（PSC，OR = 1.07，95%CI：1.00 - 1.13）、溃疡性结肠炎（UC，OR = 1.07，95%CI：1.
