Lack of association between modifiable exposures and glioma risk: A Mendelian randomisation analysis

Abstract

Abstract Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.