Plasma Ghrelin and Risks of Sex-Specific, Site-Specific, and Early-Onset Colorectal Cancer: A Mendelian Randomization Analysis.
Abstract
Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and colorectal cancer risk overall and by sex, cancer subsite, and age at diagnosis.
Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for colorectal cancer 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.
We found no evidence for an association of genetically predicted plasma total ghrelin levels and colorectal cancer 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 colorectal cancer.
Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified colorectal cancer risk.
This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with colorectal cancer risk.
EDRN PI Authors
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Medline Author List
- Albanes D
- Anderson L
- Bishop DT
- Gunter MJ
- Hazelwood E
- Le Marchand L
- Lopez Manzano C
- Murphy G
- Murphy N
- Papadimitriou N
- Peters U
- Samadder NJ
- Ulrich CM
- Van Guelpen B
- Vincent EE