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 (HRs) 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%CI 1.03-1.06), chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL: 2.79, 2.45-3.18), lung cancer (1.14, 1.08-1.20), and breast cancer (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, 1.07-1.25), and inversely with CLL/SLL (0.38, 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 white blood cells or an increased neutrophil-to-lymphocyte ratio may indicate an overly active inflammatory response, potentially contributing to the eventual onset of certain types of cancer.