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Genetically proxied impaired GIPR signaling and risk of 6 cancers

Rogers, Miranda ; Gill, Dipender ; Ahlqvist, Emma LU ; Robinson, Tim ; Mariosa, Daniela ; Johansson, Mattias ; Cortez Cardoso Penha, Ricardo ; Dossus, Laure ; Gunter, Marc J. and Moreno, Victor , et al. (2023) In iScience 26(6).
Abstract

Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship 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 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this... (More)

Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship 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 controls. 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 colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Genetics, Health sciences
in
iScience
volume
26
issue
6
article number
106848
publisher
Elsevier
external identifiers
  • pmid:37250804
  • scopus:85159892277
ISSN
2589-0042
DOI
10.1016/j.isci.2023.106848
language
English
LU publication?
yes
id
ecf7e48b-4909-44b5-93e4-53f7f82bb4f5
date added to LUP
2023-08-16 15:58:48
date last changed
2024-04-20 00:51:10
@article{ecf7e48b-4909-44b5-93e4-53f7f82bb4f5,
  abstract     = {{<p>Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship 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 controls. 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 colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. 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.</p>}},
  author       = {{Rogers, Miranda and Gill, Dipender and Ahlqvist, Emma and Robinson, Tim and Mariosa, Daniela and Johansson, Mattias and Cortez Cardoso Penha, Ricardo and Dossus, Laure and Gunter, Marc J. and Moreno, Victor and Davey Smith, George and Martin, Richard M. and Yarmolinsky, James}},
  issn         = {{2589-0042}},
  keywords     = {{Cancer; Genetics; Health sciences}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Genetically proxied impaired GIPR signaling and risk of 6 cancers}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.106848}},
  doi          = {{10.1016/j.isci.2023.106848}},
  volume       = {{26}},
  year         = {{2023}},
}