Lack of association between modifiable exposures and glioma risk: a Mendelian randomization analysis

Charlie N Saunders; Alex J Cornish; Ben Kinnersley; Philip J Law; Elizabeth B Claus; Dora Il'yasova; Joellen Schildkraut; Jill S Barnholtz-Sloan; Sara H Olson; Jonine L Bernstein; Rose K Lai; Stephen Chanock; Preetha Rajaraman; Christoffer Johansen; Robert B Jenkins; Beatrice S Melin; Margaret R Wrensch; Marc Sanson; Melissa L Bondy; Richard S Houlston

doi:10.1093/neuonc/noz209

Lack of association between modifiable exposures and glioma risk: a Mendelian randomization analysis

Neuro Oncol. 2020 Feb 20;22(2):207-215. doi: 10.1093/neuonc/noz209.

Authors

Charlie N Saunders¹, Alex J Cornish¹, Ben Kinnersley¹, Philip J Law¹, Elizabeth B Claus^{2

3}, Dora Il'yasova^{4

5

6}, Joellen Schildkraut^{5

6}, Jill S Barnholtz-Sloan⁷, Sara H Olson⁸, Jonine L Bernstein⁸, Rose K Lai⁹, Stephen Chanock¹⁰, Preetha Rajaraman¹⁰, Christoffer Johansen^{11

12}, Robert B Jenkins¹³, Beatrice S Melin¹⁴, Margaret R Wrensch^{15

16}, Marc Sanson^{17

18}, Melissa L Bondy¹⁹, Richard S Houlston²⁰

Affiliations

¹ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
² School of Public Health, Yale University, New Haven, Connecticut, USA.
³ Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Georgia State University, Atlanta, Georgia, USA.
⁵ Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
⁶ Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA.
⁷ Department of Population and Quantitative Health Sciences and the Cleveland Center for Health Outcomes Research, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
⁸ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁹ Departments of Neurology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹¹ Danish Cancer Society Research Center, Survivorship, Danish Cancer Society, Copenhagen, Denmark.
¹² Oncology Clinic, Finsen Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
¹³ Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA.
¹⁴ Department of Radiation Sciences, Umeå University, Umeå, Sweden.
¹⁵ Department of Neurological Surgery, School of Medicine, University of California San Francisco (UCSF), San Francisco, California, USA.
¹⁶ Institute of Human Genetics, University of California San Francisco, San Francisco, California, USA.
¹⁷ Sorbonne University, National Center for Scientific Research, National Institute of Health and Medical Research (INSERM), Brain and Spinal Cord Institute, Paris, France.
¹⁸ Department of Neurology Mazarin 2, Pitié-Salpêtrière Hospital Group, Paris, France.
¹⁹ Section of Epidemiology and Population Sciences, Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Division of Molecular Pathology, The Institute of Cancer Research, London, UK.

Abstract

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; andInflammatory 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.

Keywords: Mendelian randomization; cancer; glioma; risk.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms*
Diet / adverse effects
Glioma*
Humans
Inflammation / complications
Life Style
Mendelian Randomization Analysis
Metabolism / genetics
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding