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

Constantinescu, Andrei‐Emil; Bull, Caroline J.; Jones, Nick; Mitchell, Ruth; Burrows, Kimberley; Dimou, Niki; Bézieau, Stéphane; Brenner, Hermann; Buchanan, Daniel D.; D'Amato, Mauro; Jenkins, Mark A.; Moreno, Victor; Pai, Rish K.; Um, Caroline Y.; White, Emily; Murphy, Neil; Gunter, Marc; Timpson, Nicholas J.; Huyghe, Jeroen R.; Vincent, Emma E.

doi:10.1002/ijc.34691

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

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

International Journal of Cancer, Volume: 154, Issue: 1, Pages: 94 - 103

Swansea University Author: Nick Jones

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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
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa64314

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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	2024-09-17T11:13:30.4263913 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 MEDS 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 COLLEGE NANME Medical School COLLEGE CODE MEDS 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). 2024-09-17T11:13:30.4263913 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
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hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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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
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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	2024-01-01T14:33:19Z
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Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study

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