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Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis

Title: Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis
Authors: Yarmolinsky, J; Bouras, E; Constantinescu, A; Burrows, K; Bull, CJ; Vincent, EE; Martin, RM; Dimopoulou, O; Lewis, SJ; Moreno, V; Vujkovic, M; Chang, K-M; Voight, BF; Tsao, PS; Gunter, MJ; Hampe, J; Pellatt, AJ; Pharoah, PDP; Schoen, RE; Gallinger, S; Jenkins, MA; Pai, RK; consortium, PRACTICAL; Program, VA Million Veteran; Gill, D; Tsilidis, KK
Contributors: Neal, D
Publisher Information: Springer
Publication Year: 2025
Collection: Oxford University Research Archive (ORA)
Description: Aims/hypothesis: Epidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.Methods: We developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (p
Document Type: article in journal/newspaper
Language: English
DOI: 10.1007/s00125-023-05925-4
Availability: https://doi.org/10.1007/s00125-023-05925-4; https://ora.ox.ac.uk/objects/uuid:bf99e11f-b0b8-4809-8af3-ba3e08ae0340
Rights: info:eu-repo/semantics/openAccess ; CC Attribution (CC BY)
Accession Number: edsbas.D145B9CA
Database: BASE