Abstract
Systemic inflammation markers have been linked to increased cancer risk and mortality in a number of studies. However, few studies have estimated pre-diagnostic associations of systemic inflammation markers and cancer risk. Such markers could serve as biomarkers of cancer risk and aid in earlier identification of the disease. This study estimated associations between pre-diagnostic systemic inflammation markers and cancer risk in the prospective UK Biobank cohort of approximately 440,000 participants recruited between 2006 and 2010. We assessed associations between four immune-related markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for 17 cancer sites by estimating hazard ratios (HR) using flexible parametric survival models. We observed positive associations with risk for seven out of 17 cancers with SII, NLR, PLR, and negative associations with LMR. The strongest associations were observed for SII for colorectal and lung cancer risk, with associations increasing in magnitude for cases diagnosed within one year of recruitment. For instance, the HR for colorectal cancer per standard deviation increment in SII was estimated at 1.09 (95% CI 1.02–1.16) in blood drawn five years prior to diagnosis and 1.50 (95% CI 1.24–1.80) in blood drawn one month prior to diagnosis. We observed associations between systemic inflammation markers and risk for several cancers. The increase in risk the last year prior to diagnosis may reflect a systemic immune response to an already present, yet clinically undetected cancer. Blood cell ratios could serve as biomarkers of cancer incidence risk with potential for early identification of disease in the last year prior to clinical diagnosis.
Highlights
Inflammation may contribute to the incidence, tumour stage, and progression of cancer [1,2,3]
Four ratios have been highlighted by previous studies as related to morbidity and mortality, including neutrophil-to-lymphocyte ratio (NLR), plateletto-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and the systemic immune-inflammation index (SII) based on peripheral lymphocyte, neutrophil, monocyte and platelet counts [11, 14]
We aimed to evaluate the longitudinal relation between four systemic inflammation markers (SII, NLR, PLR, LMR) and site-specific cancer risk in the years leading up to diagnosis using data from UK Biobank, based on about 440,000 study participants
Summary
Inflammation may contribute to the incidence, tumour stage, and progression of cancer [1,2,3]. Tumor-infiltrating lymphocytes serve as important clinical biomarkers for patient stratification and may complement traditional prognostic indicators, such as stage and grade [4,5,6,7,8] Both the local increase in immune cell infiltration in tumors, as well as elevated systemic inflammation responses, may be important indicators of cancer progression and prognosis [9,10,11]. Four ratios have been highlighted by previous studies as related to morbidity and mortality, including neutrophil-to-lymphocyte ratio (NLR), plateletto-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and the systemic immune-inflammation index (SII) based on peripheral lymphocyte, neutrophil, monocyte and platelet counts [11, 14] These ratios have been observed related to cancer risk and mortality, the majority of these studies have investigated them as prognostic markers in newly diagnosed cancer patients and have found inconsistent results [11, 15]. Two recent studies have assessed such markers pre-diagnostically; one study reported associations between blood cell ratios and total incidence of multiple cancers [16] in a Dutch cohort, and the other between blood cell counts and lung cancer incidence using UK Biobank data [17]
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