Abstract 2250: Eosinophil-to-lymphocyte ratio and cancer risk in the UK Biobank

Abstract Background: Eosinophils exhibit anti-tumor cytotoxic responses in the tumor microenvironment. Some atopic diseases, characterized by elevated peripheral eosinophils, are inversely associated with cancer risk. The balance of atopy and immunity may be estimated by an eosinophil-to-lymphocyte ratio (ELR). This study aims to understand the role of ELR as a biomarker in carcinogenesis. Methods: We evaluated 445,404 adults aged 37-73 years at baseline in a prospective cohort study, the UK Biobank, who were cancer-free at initial assessment, had more than one year of follow-up, and had baseline white blood cell (WBC) count and differential measurements. ELR was categorized into quartiles. Incident cancers were ascertained from cancer registries from 2006-2015. Multivariable Cox regression was used to estimate per quartile ELR hazard ratios (aHRs) separately for 52 cancer sites, adjusted for age (quartiles), sex, race (white, non-white), smoking/alcohol (never, past, current), body mass index (<25, 25-30, ≥30 kg/m2) and total WBC (quartiles). Multiple comparisons were considered by a Bonferroni-corrected threshold (p<0.00096). Results: Over a median follow-up time of 6.9 years from baseline, 22,853 incident cancers were diagnosed. The median ELR was 0.07 (interquartile range=0.05-0.12). Higher ELR was inversely associated with overall cancer risk (aHR 0.98, 95%CI: 0.97-0.99; p-trend=0.0001) and chronic lymphocytic leukemia (0.50, 0.44-0.56; <0.0001). We also observed suggestive inverse ELR associations with other lymphocytic leukemia, acute and other myeloid leukemia, myeloma, melanoma and cancers of the nose/middle ear, tongue, prostate (aHR range: 0.63-0.97; p-trend<0.05). Per quartile increase of ELR was suggestively associated with increased risk of diffuse large B-cell lymphoma (aHR 1.13, 95%CI: 1.03-1.25; p-trend=0.01). Conclusion: We observed inverse associations between ELR and cancer risk in a large general population. Our findings suggest that atopy may be protective against cancer. Future research is warranted to elucidate the relationship between atopy and immunity in tumor surveillance. Impact/Significance: ELR presents a cost-effective and routinely accessible biomarker that may have implications for carcinogenesis, and may be leveraged to inform early detection of certain cancers. Citation Format: Jeanny Wang, Eric Engels, Minkyo Song. Eosinophil-to-lymphocyte ratio and cancer risk in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2250.