Genetically proxied impaired GIPR signaling and risk of 6 cancers

Ahlqvist, Emma (author): Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups

Mariosa, Daniela (author): International Agency for Research on Cancer, World Health Organization

Johansson, Mattias (author): International Agency for Research on Cancer, World Health Organization

Cortez Cardoso Penha, Ricardo (author): International Agency for Research on Cancer, World Health Organization

Dossus, Laure (author): International Agency for Research on Cancer, World Health Organization

Gunter, Marc J. (author): International Agency for Research on Cancer, World Health Organization

Moreno, Victor (author): CIBER Epidemiology and Public Health (CIBERESP),Bellvitge University Hospital-IDIBELL,University of Barcelona

Martin, Richard M. (author): University Hospitals Bristol NHS Foundation Trust,University of Bristol

(creator_code:org_t)

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Abstract Subject headings

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.

By the author/editor: Rogers, Miranda; Gill, Dipender; Ahlqvist, Emma; Robinson, Tim; Mariosa, Daniela; Johansson, Matti ...; show more...; Cortez Cardoso P ...; Dossus, Laure; Gunter, Marc J.; Moreno, Victor; Davey Smith, Geo ...; Martin, Richard ...; Yarmolinsky, Jam ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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