根据观察研究，嗜酸性粒细胞对结直肠癌（CRC）的发展起到保护作用，中性粒细胞则被认为有相关性，但因果关系尚不清楚。本研究旨在使用Mendelian随机化（MR）方法，估计循环白细胞计数对CRC风险的因果效应（N = ~550,000），其中包括嗜碱性粒细胞、嗜酸性粒细胞、单核细胞、淋巴细胞和中性粒细胞。为了比较，我们还使用了来自英国生物库（UK Biobank）的个体级数据（4043例初发CRC病例和332,773例对照组），进行了纵向队列分析。逆方差加权（IVW）MR分析表明，增加嗜碱性粒细胞计数和嗜酸性粒细胞计数对CRC风险具有保护作用[每1个标准差（SD）增加的OR：0.88，95％置信区间（CI）：0.78-0.99，P = .04；OR：0.93，95％CI：0.88-0.98，P = .01]。在考虑其他所有白细胞亚型的情况下，使用多变量MR进行基因相关性校正，嗜酸性粒细胞的保护作用仍然存在[每1个SD增加的OR：0.88，95％CI：0.80-0.97，P = .01]。调整后，淋巴细胞计数的增加对CRC风险也具有保护作用[OR：0.84，95％CI：0.76-0.93，P = 6.70e-4]。与MR结果一致，全面校正模型中的队列分析也显示了嗜酸性粒细胞的保护作用[每1个SD增加的RR：0.96，95％CI：0.93-0.99，P = .02]，以及在考虑其他白细胞亚型的情况下进行调整的结果[RR：0.96，95％CI：0.93-0.99，P = .001]。本研究显示了外周血液免疫细胞，特别是嗜酸性粒细胞和淋巴细胞在CRC发展中的作用，强调了需要进行机制研究以探究这些关系。© 2023 The Authors. International Journal of Cancer由John Wiley＆Sons Ltd代表UICC出版。

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.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.