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Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study

Andrei‐Emil Constantinescu Orcid Logo, Caroline J. Bull Orcid Logo, Nick Jones Orcid Logo, Ruth Mitchell, Kimberley Burrows, Niki Dimou, Stéphane Bézieau, Hermann Brenner, Daniel D. Buchanan Orcid Logo, Mauro D'Amato, Mark A. Jenkins, Victor Moreno Orcid Logo, Rish K. Pai, Caroline Y. Um, Emily White, Neil Murphy Orcid Logo, 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 Orcid Logo

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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...

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Published in: International Journal of Cancer
ISSN: 0020-7136 1097-0215
Published: Wiley 2024
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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. 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spelling v2 64314 2023-09-01 Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 2023-09-01 BMS 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. Journal Article International Journal of Cancer 154 1 94 103 Wiley 0020-7136 1097-0215 Colorectal cancer, eosinophils, Mendelian randomisation, UK biobank, White blood cell count 1 1 2024 2024-01-01 10.1002/ijc.34691 http://dx.doi.org/10.1002/ijc.34691 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee 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). 2024-01-08T14:01:34.7602373 2023-09-01T15:42:37.5500288 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Andrei‐Emil Constantinescu 0000-0002-7974-5245 1 Caroline J. Bull 0000-0002-2176-5120 2 Nick Jones 0000-0003-4846-5117 3 Ruth Mitchell 4 Kimberley Burrows 5 Niki Dimou 6 Stéphane Bézieau 7 Hermann Brenner 8 Daniel D. Buchanan 0000-0003-2225-6675 9 Mauro D'Amato 10 Mark A. Jenkins 11 Victor Moreno 0000-0002-2818-5487 12 Rish K. Pai 13 Caroline Y. Um 14 Emily White 15 Neil Murphy 0000-0003-3347-8249 16 Marc Gunter 17 Nicholas J. Timpson 18 Jeroen R. Huyghe 19 Emma E. Vincent 20 64314__28764__0354d775c1be428b8c3bc886f6dd8ab3.pdf 64314.VOR.pdf 2023-10-10T15:33:43.2902964 Output 1265201 application/pdf Version of Record true © 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). true eng https://creativecommons.org/licenses/by/4.0/
title Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
spellingShingle Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
Nick Jones
title_short Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
title_full Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
title_fullStr Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
title_full_unstemmed Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
title_sort Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study
author_id_str_mv 0fce0f7ddbdbfeb968f4e2f1e3f86744
author_id_fullname_str_mv 0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones
author Nick Jones
author2 Andrei‐Emil Constantinescu
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
format Journal article
container_title International Journal of Cancer
container_volume 154
container_issue 1
container_start_page 94
publishDate 2024
institution Swansea University
issn 0020-7136
1097-0215
doi_str_mv 10.1002/ijc.34691
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
url http://dx.doi.org/10.1002/ijc.34691
document_store_str 1
active_str 0
description 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.
published_date 2024-01-01T14:01:36Z
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