Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study.
Mendelian randomisation
UK biobank
White blood cell count
colorectal cancer
eosinophils
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 01 2024
01 01 2024
Historique:
revised:
06
07
2023
received:
17
04
2023
accepted:
17
07
2023
medline:
14
11
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
Observational studies have suggested a protective role for eosinophils in colorectal cancer (CRC) development and implicated neutrophils, but the causal relationships remain unclear. Here, we aimed to estimate the causal effect of circulating white blood cell (WBC) counts (N = ~550 000) for basophils, eosinophils, monocytes, lymphocytes and neutrophils on CRC risk (N = 52 775 cases and 45 940 controls) using Mendelian randomisation (MR). For comparison, we also examined this relationship using individual-level data from UK Biobank (4043 incident CRC cases and 332 773 controls) in a longitudinal cohort analysis. The inverse-variance weighted (IVW) MR analysis suggested a protective effect of increased basophil count and eosinophil count on CRC risk [OR per 1-SD increase: 0.88, 95% CI: 0.78-0.99, P = .04; OR: 0.93, 95% CI: 0.88-0.98, P = .01]. The protective effect of eosinophils remained [OR per 1-SD increase: 0.88, 95% CI: 0.80-0.97, P = .01] following adjustments for all other WBC subtypes, to account for genetic correlation between the traits, using multivariable MR. A protective effect of increased lymphocyte count on CRC risk was also found [OR: 0.84, 95% CI: 0.76-0.93, P = 6.70e-4] following adjustment. Consistent with MR results, a protective effect for eosinophils in the cohort analysis in the fully adjusted model [RR per 1-SD increase: 0.96, 95% CI: 0.93-0.99, P = .02] and following adjustment for the other WBC subtypes [RR: 0.96, 95% CI: 0.93-0.99, P = .001] was observed. Our study implicates peripheral blood immune cells, in particular eosinophils and lymphocytes, in CRC development, highlighting a need for mechanistic studies to interrogate these relationships.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
94-103Subventions
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom
Organisme : Diabetes UK
ID : 17/0005587
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N0137941/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R21CA230486
Pays : United States
Organisme : Wellcome Trust
ID : 202802/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204813/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217065/Z/19/Z
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-2001
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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