Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis
Menée à l'aide d'une méthode de randomisation mendélienne et de données d'échantillons sanguins prélevés chez 54 219 personnes ainsi que de données génétiques portant sur 86 854 témoins et 73 673 patients atteints d'un cancer colorectal, cette étude analyse l'association entre les taux de ghréline plasmatique et le risque de développer la maladie par sexe, localisation et âge au moment du diagnostic
Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis. Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. Results: We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC. Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk. Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.