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.

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