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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/201727
Genetically proxied impaired GIPR signaling and risk of 6 cancers
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Preclinical and genetic studies suggest that impaired glucose-dependent insulino-tropic polypeptide receptor (GIPR) signaling worsens glycemic control. The rela-tionship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 con-trols. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocal-ization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concen-trations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention.
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ROGERS, Miranda, GILL, Dipender, AHLQVIST, Emma, ROBINSON, Timothy m., MARIOSA, Daniela, JOHANSSON, Mattias, CORTEZ CARDOSO PENHA, Ricardo, DOSSUS, Laure, GUNTER, Marc j., MORENO AGUADO, Víctor, DAVEY SMITH, George, MARTIN, Richard m., YARMOLINSKY, James. Genetically proxied impaired GIPR signaling and risk of 6 cancers. _iScience_. 2023. Vol. 26, núm. 6. [consulta: 24 de gener de 2026]. ISSN: 2589-0042. [Disponible a: https://hdl.handle.net/2445/201727]