Back to Search
Start Over
Can NPC1L1 inhibitors reduce the risk of biliary tract cancer? Evidence from a mendelian randomization study.
- Source :
-
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2024 Sep; Vol. 56 (9), pp. 1599-1604. Date of Electronic Publication: 2024 Feb 10. - Publication Year :
- 2024
-
Abstract
- Background & Aims: Oxysterols have been implicated in biliary tract cancer (BTC), and Niemann-Pick C1-like 1 (NPC1L1) has been associated with oxysterol uptake in biliary and intestinal cells. Thus, our study aims to investigate the potential causal link between genetically proxied NPC1L1 inhibitors and the risk of BTC.<br />Methods: In this study, we employed two genetic instruments as proxies for NPC1L1 inhibitors, which included LDL cholesterol-associated genetic variants located within or in close proximity to the NPC1L1 gene, as well as expression quantitative trait loci (eQTLs) of the NPC1L1 gene. Effect estimates were calculated using the Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods.<br />Results: In MR analysis using the IVW method, both proxy instruments from the UK Biobank and the GLGC demonstrated a positive association between NPC1L1-mediated LDL cholesterol and BTC risk, with odds ratios (OR) of 10.30 (95% CI = 1.51-70.09; P = 0.017) and 5.61 (95% CI = 1.43-21.91; P = 0.013), respectively. Moreover, SMR analysis revealed a significant association between elevated NPC1L1 expression and increased BTC risk (OR = 1.19, 95% CI = 1.04-1.37; P = 0.014).<br />Conclusions: This MR study suggests a causal link between NPC1L1 inhibition and reduced BTC risk. NPC1L1 inhibitors, like ezetimibe, show potential for chemoprevention in precancerous BTC patients, requiring further clinical investigation.<br />Competing Interests: Conflict of interest The authors declare no conflicts of interest.<br /> (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Humans
Quantitative Trait Loci
Polymorphism, Single Nucleotide
Ezetimibe therapeutic use
Anticholesteremic Agents therapeutic use
Anticholesteremic Agents pharmacology
Mendelian Randomization Analysis
Membrane Transport Proteins genetics
Biliary Tract Neoplasms genetics
Membrane Proteins genetics
Cholesterol, LDL blood
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3562
- Volume :
- 56
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 38342741
- Full Text :
- https://doi.org/10.1016/j.dld.2024.01.211