Abstract

Abstract Background: The neutrophil-to-lymphocyte ratio (NLR), a ratio between neutrophil and lymphocyte counts in peripheral blood, is a measure of the balance between systemic levels of inflammation and immunity. NLR has been associated with cancer prognosis, but the role of NLR as a biomarker in carcinogenesis is not well established. Methods: We evaluated 445,443 adults in the UK Biobank, who were aged 37-73 years at baseline, had measured differential blood counts, and were cancer-free and under follow-up 1 year after baseline. NLR was categorized into quartiles. Incident cancers were ascertained from cancer registries. Multivariable Cox regression was used to estimate the per quartile hazard ratio (HR), separately for 69 cancer sites. Models were adjusted for age (quartile), sex, ethnicity (white vs non-white), total WBC (quartile), smoking (never, past, current), alcohol drinking (never, past, current), and BMI (<25, 25-30, ≥30 kg/m2). We present nominally significant results (p<0.05) and also accounting for multiple comparison using a Bonferroni cutoff (p=0.00072). Results: 26,294 incident cancers were diagnosed during a median of 3.3 years of follow-up. The mean NLR in the population was 2.3 (standard deviation 1.2). Increasing NLR quartile was associated with increased risk of cancers in esophagus, colon, lung, soft tissue including heart, uterus, and kidney, but decreased risk of myeloma and chronic lymphocytic leukemia [CLL] (ptrend<0.05). Compared with the lowest NLR quartile, the highest NLR quartile was significantly associated with risk of cancers of the soft tissue including heart (HR 1.98, 95%CI 1.15-3.42), kidney (1.54, 1.22-1.94), uterus (1.39, 1.11-1.73), esophagus (1.27, 0.96-1.69), colon (1.22, 1.06-1.41), myeloma (0.63, 0.47-0.86) and CLL (0.11, 0.02-0.48). After Bonferroni correction, NLR associations remained significant for kidney cancer and CLL. Conclusion: In a comprehensive analysis in a large population-based cohort, NLR was associated with subsequent risk of several cancer types. NLR may reflect the excessive inflammatory status of an individual, even in a subclinical condition, which may promote the development of cancer. On the other hand, low NLR represents a relative rise in the lymphocytes, which may be an indication of circulating premalignant cells for lymphoid malignancies. Citation Format: Minkyo Song, Eric A. Engels. Neutrophil-to-lymphocyte ratio and subsequent cancer risk in the UK Biobank [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 752.

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