Abstract
Eosinophils exhibit anti-tumor cytotoxic responses in the tumor microenvironment and may contribute to tumor immunosurveillance. To assess the relationship between circulating eosinophils and cancer risk, we analyzed data from 443,542 adults aged 38-73 in the UK Biobank, who were initially cancer-free, had over a year of follow-up, and baseline white blood cell count measurements. Using multivariable Cox regression, we estimated hazard ratios (aHR) and 95% confidence intervals (95%CI) for each quartile increase in absolute eosinophil count (AEC) across 58 cancer types, adjusting for relevant confounders. During a median follow-up of 5.8 years, 22,747 incident cancer cases were diagnosed. We observed an inverse association, which met Bonferroni significance, between AEC and overall cancer risk (aHR, 95%CI 0.97, 0.95-0.98). Notably, 16 cancer types showed borderline associations (p <.05) with AEC, with 12 types displaying an inverse relationship. These included four hematologic cancers (acute and other myeloid leukemia, other lymphocytic leukemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma; aHR range; 0.58-0.87) and eight nonhematologic cancers (melanoma and nose/middle ear, soft tissue/heart, gum/other mouth, tongue, lung, colon, and breast cancers; aHR range: 0.65-0.95). Higher AEC showed a borderline significant association with increased risk for intrahepatic bile duct cancer, Hodgkin lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukemia (aHR range: 1.13-1.42). Our study, the largest to date, provides insights into the relationship between blood eosinophils and a comprehensive list of incident cancers. The inverse association between AEC and overall cancer risk suggests a protective role for eosinophils in tumor surveillance.