Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer.
Colorectal cancer
Diet
Fibre
GWAS
Gene-environment interaction
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
14 May 2024
14 May 2024
Historique:
received:
11
09
2023
revised:
15
04
2024
accepted:
19
04
2024
medline:
16
5
2024
pubmed:
16
5
2024
entrez:
15
5
2024
Statut:
aheadofprint
Résumé
Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. The 3-DF joint test revealed two significant loci with p-value <5 × 10 We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.
Sections du résumé
BACKGROUND
BACKGROUND
Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations.
METHODS
METHODS
A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously.
FINDINGS
RESULTS
The 3-DF joint test revealed two significant loci with p-value <5 × 10
INTERPRETATION
CONCLUSIONS
We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings.
FUNDING
BACKGROUND
National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.
Identifiants
pubmed: 38749303
pii: S2352-3964(24)00181-6
doi: 10.1016/j.ebiom.2024.105146
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105146Informations de copyright
Copyright © 2024. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of interests ESK is a co-investigator in a grant from National Institutes of Health (R01CA196569). JW is Stock shareholder of Gilead Sciences Inc. AK has received consulting fees for Illumina Inc., has participated on data safety monitoring boards or advisory boards of TensorBio, PatchBio, Serimmune, and OpenTargets, and has stock or stock options of Illumina, Freenome, Deep Genomics, Immunai, TensorBio, PatchBio, and Serimmune. MCS was a co-investigator in a grant from National Institutes of Health (R01CA201407). VM has received grant support from Instituto de Salud Carlos III and Fundacion Cientifica Asociación Española Contra el Cáncer. SBG is a co-founder of Brogent international LLC. JPL has received additional grant support (5P01CA196569, 6R01CA201407). The remaining authors declare that they have no conflicts of interest.