The role of growth factors and inflammation in the onset of glioma is poorly understood, and conflicting reports of associations of circulating IGF-1 and inflammatory biomarkers with glioma risk exist in the literature. We examined associations between C-reactive protein (CRP), white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and insulin-like growth factor-1 (IGF-1) and glioma risk in the UK Biobank cohort.
Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to circulating biomarkers concentrations were calculated using Cox proportional hazards regression, adjusted for age, sex, race, and education. Analyses were conducted separately for glioma overall and by glioma subtype.
We identified 417 incident glioma cases among 428,537 participants with 3,255,815 person-years of follow up. Weak, non-significant associations were observed with increasing levels of these biomarkers for risk of glioma overall or by glioma subtype. Among women only, IGF-1 in the highest quartile was positively associated with glioma risk compared to the lowest quartile (HR=1.64, 95%CI: 1.03–2.60, p-trend=0.08), as was NLR (HR=1.54, 95%CI: 1.00–2.39, p-trend=0.05).
In this prospective cohort, we found no significant associations between the inflammatory biomarkers CRP and WBC and the development of glioma. NLR and IGF-1 were associated with risk in women, but not men. When considered with previous studies, further investigation of NLR and IGF-1 as markers of glioma risk appears warranted, particularly in women.
This was a large study of more than 400,000 participants in the UK Biobank.
There were no significant associations between CRP and WBC and later risk of glioma.
Higher NLR and IGF-1 were associated with higher risk in women, but not in men.
Gliomas are tumors arising from the glial cells of the brain and comprise 80% of all primary adult brain tumors. The etiology of gliomas is not well understood, and ionizing radiation remains the only well-validated environmental risk factor for glioma . Men are at substantially higher risk of developing glioma than women, with a male:female ratio of approximately 1.58 for glioblastoma, the highest grade form .
Chronic inflammation has been linked to a higher risk of some cancer sites; however, the causal mechanisms underlying these relationships are not fully understood . The role of inflammation in the incidence of glioma remains poorly studied . Blood levels of C-reactive protein (CRP) are a general marker of systemic inflammation, and CRP has been positively associated with increased risk of cancers of other sites, including prostate and colorectal, in some, though not all, studies . Most studies of CRP and glioma were retrospective in design and subject to bias, or examined associations with prognosis after diagnosis rather than associations with risk .
Increases in white blood cell count (WBC) due to injury or stress represent an additional marker of inflammation; the neutrophil-to-lymphocyte ratio (NLR) may better reflect the balance of innate and adaptive immunity and may be more reproducible than WBC . NLR has been positively associated with risk of other cancers, including lung , breast , and overall cancer risk . Elevated NLR has been associated with poor overall survival in glioma patients , though no study has evaluated its relationship with glioma risk.
Insulin-like growth factor-1 (IGF-1) is part of a family of hormones that regulate normal cell growth and development. Some studies have suggested that IGF-1 also plays a role in suppressing inflammation . The role of IGF-1 in glioma development is unclear, with mixed results in previous case-control studies . In a prospective, nested case-control study of 280 patients with glioma in the European Prospective Investigation of Cancer and Nutrition (EPIC) cohort, higher levels of IGF-1 were positively associated with low-grade glioma (LGG) risk, but not with glioma overall .
To shed further light on the role of IGF-1 and systemic inflammation in glioma risk, we examined the association of related circulating biomarkers, specifically CRP, WBC, NLR, and IGF-1, with glioma risk in the UK Biobank.