Abstract
BACKGROUND: The peripheral white blood cell (WBC) and neutrophil-to-lymphocyte ratio (NLR) reflect levels of inflammation and adaptive immunity. They are associated with cancer prognosis, but their associations with cancer incidence are not established. METHODS: We evaluated 443,540 cancer-free adults in the UK Biobank with data on total WBC and its subsets, follow-up starting one year after baseline. Cox regression was used to estimate hazard ratios (HR) per quartile of WBC or NLR for incidence of 73 cancer types. RESULTS: 22,747 incident cancers were diagnosed during a median of 6.9 years of follow-up. WBC was associated with risk of cancer overall [HR, 1.05; 95% confidence interval (CI), 1.03-1.06], chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL, 2.79; 95% CI, 2.45-3.18), lung cancer (1.14, 95% CI, 1.08-1.20), and breast cancer (95% CI, 1.05-1.02-1.08). NLR was positively associated with cancer overall (HR, 1.03; 95% CI, 1.02-1.04, per quartile) and kidney cancer (1.16; 95% CI, 1.07-1.25), and inversely with CLL/SLL (0.38; 95% CI, 0.33-0.42). CONCLUSIONS: High WBC or NLR may reflect excessive inflammatory status, promoting development of some cancers. Conversely, low NLR indicates a relative rise in lymphocytes, which could reflect an increase in circulating premalignant cells before CLL/SLL diagnosis. Peripheral WBC and NLR, in combination with other clinical information or biomarkers, may be useful tools for cancer risk stratification. IMPACT: Elevated levels of WBCs or an increased NLR may indicate an overly active inflammatory response, potentially contributing to the eventual onset of certain types of cancer.