TY - JOUR

T1 - Lack of association between modifiable exposures and glioma risk

T2 - A Mendelian randomization analysis

AU - Saunders, Charlie N.

AU - Cornish, Alex J.

AU - Kinnersley, Ben

AU - Law, Philip J.

AU - Claus, Elizabeth B.

AU - Il'yasova, Dora

AU - Schildkraut, Joellen

AU - Barnholtz-Sloan, Jill S.

AU - Olson, Sara H.

AU - Bernstein, Jonine L.

AU - Lai, Rose K.

AU - Chanock, Stephen

AU - Rajaraman, Preetha

AU - Johansen, Christoffer

AU - Jenkins, Robert B.

AU - Melin, Beatrice S.

AU - Wrensch, Margaret R.

AU - Sanson, Marc

AU - Bondy, Melissa L.

AU - Houlston, Richard S.

PY - 2020

Y1 - 2020

N2 - Background: The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian randomization (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 insulin-like growth factor 1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamins (A1, B12, B6, E, and 25-hydroxyvitamin D), fatty acid levels (monounsaturated, omega-3, and omega-6) and circulating fetuin-A; Cardiometabolic factors - birth weight, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, glycated hemoglobin levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio; and Inflammatory factors - C-reactive protein, plasma interleukin-6 receptor subunit alpha and serum immunoglobulin E. Results: After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism, no significant association with glioma risk was observed (ie, 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.

AB - Background: The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian randomization (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 insulin-like growth factor 1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamins (A1, B12, B6, E, and 25-hydroxyvitamin D), fatty acid levels (monounsaturated, omega-3, and omega-6) and circulating fetuin-A; Cardiometabolic factors - birth weight, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, glycated hemoglobin levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio; and Inflammatory factors - C-reactive protein, plasma interleukin-6 receptor subunit alpha and serum immunoglobulin E. Results: After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism, no significant association with glioma risk was observed (ie, 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.

KW - cancer

KW - glioma

KW - Mendelian randomization

KW - risk

U2 - 10.1093/neuonc/noz209

DO - 10.1093/neuonc/noz209

M3 - Review

C2 - 31665421

AN - SCOPUS:85081141216

VL - 22

SP - 207

EP - 215

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 2

ER -