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Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
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Caroline J. Bull ,
Nick Jones ,
Ruth Mitchell,
Kimberley Burrows,
Niki Dimou,
Stéphane Bézieau,
Hermann Brenner,
Daniel D. Buchanan ,
Mauro D'Amato,
Mark A. Jenkins,
Victor Moreno ,
Rish K. Pai,
Caroline Y. Um,
Emily White,
Neil Murphy ,
Marc Gunter,
Nicholas J. Timpson,
Jeroen R. Huyghe,
Emma E. Vincent
International Journal of Cancer, Volume: 154, Issue: 1, Pages: 94 - 103
Swansea University Author:
Nick Jones
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© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. Distributed under the terms of a Creative Commons Attribution 4.0 License (CC BY 4.0).
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DOI (Published version): 10.1002/ijc.34691
Abstract
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 basophil...
| Published in: | International Journal of Cancer |
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| ISSN: | 0020-7136 1097-0215 |
| Published: |
Wiley
2024
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa64314 |
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| Abstract: |
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. |
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| Keywords: |
Colorectal cancer, eosinophils, Mendelian randomisation, UK biobank, White blood cell count |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Cancer Research UK (Grant Number: C18281/A29019), Diabetes UK (Grant Number: 17/0005587), Medical Research Council (Grant Numbers: MC_UU_00011/1, MC_UU_00011/4, MR/N0137941/1), National Cancer Institute (Grant Number: R21CA230486), NIHR Bristol Biomedical Research Centre (Grant Number: BRC-1215-2001), Wellcome Trust (Grant Numbers: 202802/Z/16/Z, 204813/Z/16/Z, 217065/Z/19/Z), World Cancer Research Fund International (Grant Number: IIG_2019_2009). |
| Issue: |
1 |
| Start Page: |
94 |
| End Page: |
103 |