Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts.
Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case–control study to examine these same associations.
In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89–1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32–3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61–2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG.
In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Ostrom QT, Adel Fahmideh M, Cote DJ et al (2019) Risk factors for childhood and adult primary brain tumors. Neuro-oncology 21:1357–1375
Cote DJ, Rosner BA, Smith-Warner SA, Egan KM, Stampfer MJ (2019) Statin use, hyperlipidemia, and risk of glioma. Eur J Epidemiol 34:997–1011
Smith GD, Shipley MJ (1989) Plasma cholesterol concentration and primary brain tumours. BMJ (Clin Res Ed) 299:26–27
Neugut AI, Fink DJ, Radin D (1989) Serum cholesterol and primary brain tumours: a case–control study. Int J Epidemiol 18:798–801
Abramson ZH, Kark JD (1985) Serum cholesterol and primary brain tumours: a case–control study. Br J Cancer 52:93–98
Smith GD, Neaton JD, Ben-Shlomo Y, Shipley M, Wentworth D (1992) Serum cholesterol concentration and primary malignant brain tumors: a prospective study. Am J Epidemiol 135:259–265
Knekt P, Reunanen A, Teppo L (1991) Serum cholesterol concentration and risk of primary brain tumours. BMJ (Clin Res Ed) 302:90
Saunders CN, Cornish AJ, Kinnersley B et al (2020) Lack of association between modifiable exposures and glioma risk: a Mendelian randomization analysis. Neuro-oncology 22:207–215
Ganna A, Ingelsson E (2015) 5 year mortality predictors in 498,103 UK Biobank participants: a prospective population-based study. Lancet 386:533–540
Collins R (2012) What makes UK Biobank special? Lancet 379:1173–1174
Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820
Elliott P, Peakman TC (2008) The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine. Int J Epidemiol 37:234–244
Fry D, Almond R, Moffat S, Gordon M, Singh P (2019) UK Biobank Biomarker Project: companion document to accompany serum biomarker data. UK Biobank Biomarker Panel, Oxford
Wolpin BM, Chan AT, Hartge P et al (2009) ABO blood group and the risk of pancreatic cancer. J Natl Cancer Inst 101:424–431
Khalili H, Wolpin BM, Huang ES et al (2011) ABO blood group and risk of colorectal cancer. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cospons Am Soc Prev Oncol 20:1017–1020
Belanger CF, Hennekens CH, Rosner B, Speizer FE (1978) The nurses’ health study. Am J Nurs 78:1039–1040
Smith-Warner SA, Spiegelman D, Ritz J et al (2006) Methods for pooling results of epidemiologic studies: the Pooling Project of Prospective Studies of Diet and Cancer. Am J Epidemiol 163:1053–1064
Mayers JR, Wu C, Clish CB et al (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193–1198
Hamada T, Yuan C, Bao Y et al (2019) Prediagnostic leukocyte telomere length and pancreatic cancer survival. Cancer Epidemiol Biomark Prev 28:1868–1875
Yuan C, Qian ZR, Babic A et al (2016) Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival. J Clin Oncol Off J Am Soc Clin Oncol 34:2899–2905
Stampfer MJ, Willett WC, Speizer FE et al (1984) Test of the National Death Index. Am J Epidemiol 119:837–839
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Yarmolinsky J, Wade KH, Richmond RC et al (2018) Causal inference in cancer epidemiology: what is the role of Mendelian randomization? Cancer Epidemiol Biomark Prev 27:995–1010
Villa GR, Hulce JJ, Zanca C et al (2016) An LXR-cholesterol axis creates a metabolic co-dependency for brain cancers. Cancer Cell 30:683–693
An Y, Zhang DD, Yu HL et al (2017) 27-Hydroxycholesterol regulates cholesterol synthesis and transport in C6 glioma cells. Neurotoxicology 59:88–97
Bjorkhem I, Meaney S (2004) Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 24:806–815
Hayashi H, Campenot RB, Vance DE, Vance JE (2004) Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem 279:14009–14015
Cordova CM, Schneider CR, Juttel ID, Cordova MM (2004) Comparison of LDL-cholesterol direct measurement with the estimate using the Friedewald formula in a sample of 10,664 patients. Arq bras cardiol 83(482–487):76–81
The work is based on the UK Biobank Resource under Application Number 16944. We would like to thank the participants and staff of the Nurses’ Health Study and Health Professionals Follow-Up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data.
National Institutes of Health (NIH) PO1 CA87969, U01 CA167552, UM1 CA186107, UM1 CA176726, UM1 CA167552, F30 CA235791 (DJC), the Nutrition Round Table of the Harvard T.H. Chan School of Public Health, and the H. Lee Moffitt Cancer Center and Research Institute (P30 CA076292).
Conflict of interest
Nothing to disclose.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Cote, D.J., Smith-Warner, S.A., Creed, J.H. et al. Circulating lipids and glioma risk: results from the UK Biobank, Nurses’ Health Study, and Health Professionals Follow-Up Study. Cancer Causes Control (2021). https://doi.org/10.1007/s10552-021-01391-8
- UK Biobank