Key result
Genetically higher eosinophil count is linked to a ~7% lower risk of colorectal cancer.
Why the study?
Observational studies have suggested a protective role for eosinophils in colorectal cancer development and implicated neutrophils, but the causal relationships remain unclear.
Do increased circulating white blood cell counts reduce the risk of colorectal cancer?
Observational (n=550,000)
Do increased circulating white blood cell counts reduce the risk of colorectal cancer?
Genetically predicted and observationally measured increases in eosinophil and lymphocyte counts are associated with a reduced risk of colorectal cancer.
Should not yet change colorectal cancer prevention practice; leaves open whether eosinophil-modifying interventions affect incidence.
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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Constantinescu et al. (2023) conducted an observational in Colorectal cancer (n=550,000). Circulating white blood cell counts (eosinophils, basophils, lymphocytes) was evaluated on Colorectal cancer risk (OR 0.93, 95% CI 0.88-0.98, p=.01). Genetically predicted higher eosinophil count was associated with a reduced risk of colorectal cancer (OR per 1-SD increase 0.93; 95% CI 0.88-0.98; P=0.01).
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