Genetic associations of cholelithiasis and biliary tract cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-18 DOI:10.1016/j.tranon.2025.102533

Yong Jiang , Huimou Chen , Qing Tian , Chonghui Hu , Zhengyu Wu , Yuan Yuan , Xueliang Ouyang , Kunlong Chang , Daixin Wu , Juncheng Chen , Junwei Huang , Rufu Chen , Shangyou Zheng , Li Li

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引用次数: 0

Abstract

Biliary tract cancer (BTC) is highly malignant and more prevalent in populations with cholelithiasis, but the underlying mechanisms remain unclear. This study aimed to investigate the potential genetic links between cholelithiasis and BTC. We first employed single- and two-sample Mendelian randomization to assess whether the association between cholelithiasis and BTC incidence was influenced by confounding factors, revealing a significant association between cholelithiasis and BTC (P < 0.05). Multi-trait analysis of GWAS identified five novel lead genomic risk loci for BTC, with functional mapping and annotation performed using FUMA. Colocalization analysis using quantitative trait loci data highlighted shared signals for LRPPRC and ABCG5 in liver tissue. Additionally, in individuals without cholelithiasis, genetic loci rs6741243 and rs7599981 were associated with an increased BTC risk (both P < 0.05) in a Cox regression model. Gene expression analysis further supported these findings, showing significant upregulation of LRPPRC (P < 0.001) and downregulation of ABCG5 (P < 0.001) in BTC tissues, confirming their roles in carcinogenesis. This study provides compelling evidence for a genetic association between cholelithiasis and BTC, highlighting the role of genetic variants in ABCG5/8 and LRPPRC in mediating these conditions.

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胆石症与胆道癌的遗传关系。

胆道癌（BTC）是高度恶性的，在胆石症人群中更为普遍，但其潜在机制尚不清楚。本研究旨在探讨胆石症与BTC之间潜在的遗传联系。我们首先采用单样本和双样本孟德尔随机化来评估胆石症和BTC发病率之间的关联是否受混杂因素的影响，结果显示胆石症和BTC之间存在显著相关性（P < 0.05）。GWAS的多性状分析确定了BTC的5个新的先导基因组风险位点，并使用fua进行了功能定位和注释。利用定量性状位点数据进行共定位分析，发现肝组织中LRPPRC和ABCG5的共享信号。此外，在没有胆石症的个体中，基因位点rs6741243和rs7599981与BTC风险增加相关（均P < 0.05）。基因表达分析进一步支持了这些发现，在BTC组织中，LRPPRC显著上调（P < 0.001）， ABCG5显著下调（P < 0.001），证实了它们在癌变中的作用。这项研究为胆石症和BTC之间的遗传关联提供了令人信服的证据，强调了ABCG5/8和LRPPRC基因变异在介导这些疾病中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.