Journal Article

DKFZ-2023-01656

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study.

Constantinescu, A.-E. ; Bull, C. J. ; Jones, N. ; Mitchell, R. ; Burrows, K. ; Dimou, N. ; Bézieau, S. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; D'Amato, M. ; Jenkins, M. A. ; Moreno, V. ; Pai, R. K. ; Um, C. Y. ; White, E. ; Murphy, N. ; Gunter, M. ; Timpson, N. J. ; Huyghe, J. R. ; Vincent, E. E.

2024
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi: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 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.

Keyword(s): Mendelian randomisation ; UK biobank ; White blood cell count ; colorectal cancer ; eosinophils

Note: 2024 Jan 1;154(1):94-103

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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