Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk.

Autor:	Larsson SC; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Höijer J; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Sun J; Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Li X; Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Burgess S; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom., Michaëlsson K; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2023 Dec 01; Vol. 32 (12), pp. 1771-1776.
DOI:	10.1158/1055-9965.EPI-23-0757
Abstrakt:	Background: Observational studies have suggested that the gut hormone ghrelin is an early marker of future risk of developing gastrointestinal cancer. However, whether ghrelin is a causal risk factor remains unclear. We conducted a genome-wide association study (GWAS) of plasma ghrelin and used Mendelian randomization (MR) to investigate the possible causal association between ghrelin and gastrointestinal cancer risk. Methods: Genetic variants associated with plasma ghrelin were identified in a GWAS comprising 10,742 Swedish adults in the discovery (N = 6,259) and replication (N = 4,483) cohorts. The association between ghrelin and gastrointestinal cancer was examined through a two-sample MR analysis using the identified genetic variants as instruments and GWAS data from the UK Biobank, FinnGen, and a colorectal cancer consortium. Results: GWAS found associations between multiple genetic variants within ±200 kb of the GHRL gene and plasma ghrelin. A two-sample MR analysis revealed that genetically predicted higher plasma ghrelin levels were associated with a lower risk of gastrointestinal cancer in UK Biobank and in a meta-analysis of the UK Biobank and FinnGen studies. The combined OR per approximate doubling of genetically predicted plasma ghrelin was 0.91 (95% confidence interval, 0.85-0.99; P = 0.02). Colocalization analysis revealed limited evidence of shared causal variants for plasma ghrelin and gastrointestinal cancer at the GHRL locus (posterior probability H4 = 24.5%); however, this analysis was likely underpowered. Conclusions: Our study provides evidence in support of a possible causal association between higher plasma ghrelin levels and a reduced risk of gastrointestinal cancer. Impact: Elevated plasma ghrelin levels might reduce the risk of gastrointestinal cancer. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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