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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.

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Introduction: The risk for cancer may be elevated in patients with inflammatory bowel disease (IBD) due to chronic inflammation caused by IBD and/or immunosuppressive treatments. A comprehensive investigation of cancer as a complication of IBD in elderly patients is needed, as this population has a high background risk of cancer and are underrepresented in IBD studies. Methods: We performed a case-control study using Surveillance Epidemiology and End Results-Medicare linked data. Cancer cases (N=1,986,735) included all patients aged 66-99 with a first invasive neoplasm diagnosed in 1992-2015. Cancer-free controls (N=200,000) were randomly selected from Medicare and matched by sex, age, and selection year. Medicare claims containing ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes occurring at least one year prior to selection were used to identify IBD patients. We estimated odds ratios (OR) and 95% confidence intervals (CI) with logistic regression, adjusting for the matching factors, race, and the average number of physician visits per year. A Bonferroni-corrected threshold of significance was defined as p < 0.0003 for 156 tests. Colorectal cancer analyses were further adjusted for the average number of colorectal cancer screens per year occurring at least one year before selection. Results: IBD, CD, and UC were present in 0.80%, 0.33%, and 0.53% of cancer cases and in 0.76%, 0.30%, and 0.52% of controls, respectively. Out of 52 cancers examined, IBD was significantly associated with cancers of the small intestine (OR=2.53; 95% CI=2.14-2.99), intrahepatic (1.93; 1.48-2.52) and extrahepatic bile ducts (1.73; 1.37-2.19), rectum (1.67; 1.43-1.94), colon (1.20; 1.10-1.31), and lung (1.14; 1.07-1.23). For hematological malignancies, IBD was significantly associated with myelodysplastic syndrome (MDS) (OR=1.45; 95% CI=1.28-1.65) and diffuse large B-cell lymphoma (DLBCL) (1.28; 1.13-1.46). An inverse association was observed for IBD and cancer of the uterus (0.72; 0.62-0.83). CD was associated with cancers of the small intestine (OR= 4.21; 95% CI= 3.40-5.22), myelodysplastic syndrome (1.74; 1.44-2.11), rectum (1.60; 1.1.26-2.03), and lung (1.29; 1.16-1.43) and. UC was associated with cancers of the gastrointestinal system: intrahepatic bile ducts (1.94; 1.41-2.67), rectum (1.88; 1.57-2.25), and colon (1.38; 1.25-1.53). Conclusions: Our large population-based analysis evaluating a comprehensive range of cancers found IBD significantly associated with increased risk for cancers of the small intestine, biliary tract, colorectum, and lung. IBD was also associated with DLBCL and MDS. Positive associations with IBD and cancers of the gastrointestinal system may reflect complications of chronic inflammation, while associations with DLBCL and MDS may reflect the effect of immunosuppressive medications. Citation Format: Jeanny Wang, Monica D'Arcy, Eric Engels, Minkyo Song. Associations of inflammatory bowel disease and subsequent cancers in the United States elderly population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 753.