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

Saunders, Charlie N; Cornish, Alex J.; Kinnersley, Ben; Law, Philip; Claus, Elizabeth B.; Il’yasova, Dora; Schildkraut, Joellen M.; Barnholtz‐Sloan, Jill S.; Bernstein, Jonine L.; Lai, Rose; Chanock, Stephen J.; Rajaraman, Preetha; Johansen, Christoffer; Jenkins, Robert B.; Melin, Beatrice; Wrensch, Margaret; Sanson, Marc; Bondy, Melissa L.; Houlston, Richard S.

doi:10.1093/neuonc/noz209

Cited by 32 publications

(37 citation statements)

References 37 publications

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“…While obesity is a well-known risk factor for the development of various types of cancer [7,8], conflicting results have been reported concerning the relationship between obesity and the risk of glioma in prospective cohort studies, case-control studies, and metaanalyses [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, a recent biological study suggested that adipocyte-released factors can promote the growth and progression of glioma cells [24].…”

Section: Introductionmentioning

confidence: 99%

Associations of General and Abdominal Obesity with the Risk of Glioma Development

Ahn

Han

Lee

et al. 2021

Cancers

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The association between obesity and the risk of glioma remains unclear. We sought to evaluate the potential association between general and abdominal obesity and the risk of glioma based on a nationwide population-based cohort study of Koreans. Using data from the Korean National Health Insurance System cohort, 6,833,744 people older than 20 years who underwent regular national health examination in both 2009 and 2011 were followed until the end of 2017. We documented 4771 glioma cases based on an ICD-10 code of C71 during the median follow-up period of 7.30 years. Individuals with a body mass index (BMI) ≥ 25.0 kg/m2 were at significantly higher risk of developing glioma than those with a BMI < 25.0 kg/m2 (HR 1.08 CI 1.02–1.15). Individuals with a waist circumference (WC) ≥ 90 cm (males)/85 cm (females) also had a significantly higher risk of glioma than those with a WC < 90 cm (males)/85 cm (females) (HR 1.16 CI 1.09–1.24). In the group with a BMI ≥ 25.0 kg/m2, individuals with abdominal obesity were at significantly higher risk of developing glioma (HR 1.18 CI 1.09–1.27) than those without abdominal obesity. The role of abdominal obesity in this association was stronger in women than in men. To the best of our knowledge, this is the first demonstration that obese people may be at higher risk of glioma, especially centrally obese people from an Asian population with a BMI ≥ 25.0 kg/m2. Loss of visceral fat in people with abdominal obesity may reduce their risk of developing glioma.

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Section: Introductionmentioning

confidence: 99%

Associations of General and Abdominal Obesity with the Risk of Glioma Development

Ahn

Han

Lee

et al. 2021

Cancers

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“…Several cohort studies, case-control studies, and meta-analyses have evaluated the associations between adiposity and gliomas; however, the results from these studies have been inconclusive. While the majority of these studies have reported null associations [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], three studies reported positive associations [14,18,22]; one meta-analysis study found that there was a significant association between adiposity and glioma development in females [14], while one cohort study and one case-control study found that elevated BMI in early adulthood was significantly associated with increased risk of gliomas [18,22]. These…”

Section: Discussionmentioning

confidence: 96%

“…In addition, we found a stronger association between abdominal obesity and the risk of glioma development than BMI and the risk of glioma development. Our study included a large number of glioma cases (n=4,771) and is the second largest study to evaluate the association between obesity and glioma risk [9].…”

Section: Discussionmentioning

confidence: 99%

“…While obesity is a well-known risk factor for developing various types of cancer [7,8], conflicting results have been reported concerning the relationship between obesity and the risk of glioma in prospective cohort studies, case-control studies, and meta-analyses [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, a recent biological study suggested that adipocyte-released factors can promote the growth and progression of glioma cells [24].…”

Section: Introductionmentioning

confidence: 99%

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Associations of General and Abdominal Obesity with the Risk of Glioma Development

Ahn

Han²,

Lee³

et al. 2021

Preprint

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The association between obesity and the risk of gliomas remains unclear. We sought to evaluate the potential association between general and abdominal obesity and the risk of gliomas based on a nationwide population-based cohort study of Koreans. Using data from the Korean National Health Insurance System cohort, 6,833,744 people older than 20 years who underwent regular national health examination in both 2009 and 2011 were followed until the end of 2017. We documented 4,771 glioma cases based on an ICD-10 code of C71 during the median follow-up period of 7.30 years. Individuals with a body mass index (BMI) ≥ 25.0 kg/m2 were at significantly higher risk of gliomas than those with a BMI < 25.0 kg/m2 (HR 1.08 CI 1.02-1.15). Individuals with a waist circumference (WC) ≥ 90 cm (males)/85 cm (females) also had a significantly higher risk of gliomas than those with a WC < 90 cm (males)/85 cm (females) (HR 1.16 CI 1.09-1.24). In the group with a BMI ≥ 25.0 kg/m2, individuals with abdominal obesity were at significantly higher risk of gliomas (HR 1.18 CI 1.09-1.27) than those without abdominal obesity. The role of abdominal obesity in this association was stronger in women than in men. To our knowledge, this is the first demonstration that obese people may be at higher risk of gliomas, especially centrally obese people from an Asian population with a BMI ≥ 25.0 kg/m2. Loss of visceral fat in people with abdominal obesity may reduce their risk of gliomas.

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“…16 After finding no strong associations, we subsequently investigated a more comprehensive list of dietary and lifestyle factors that commonly influence the risk of other cancers, again finding no evidence for strong associations. 17 Other researchers have used MR to examine the relationship between glioma and other traits with more success, purporting a strong association with leukocyte telomere length. 18,19 All of these MR analyses have, however, been predicated on assumptions about disease aetiology.…”

Section: Introductionmentioning

confidence: 99%

Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study

et al. 2020

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Background The aetiology of glioma is poorly understood. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to search for glioma risk factors. Methods We performed an MR-PheWAS analysing 316 phenotypes, proxied by 8387 genetic variants, and summary genetic data from a GWAS of 12,488 glioma cases and 18,169 controls. Causal effects were estimated under a random-effects inverse-variance-weighted (IVW-RE) model, with robust adjusted profile score (MR-RAPS), weighted median and mode-based estimates computed to assess the robustness of findings. Odds ratios per one standard deviation increase in each phenotype were calculated for all glioma, glioblastoma (GBM) and non-GBM tumours. Results No significant associations (P < 1.58 × 10−4) were observed between phenotypes and glioma under the IVW-RE model. Suggestive associations (1.58 × 10−4 < P < 0.05) were observed between leukocyte telomere length (LTL) with all glioma (ORSD = 3.91, P = 9.24 × 10−3) and GBM (ORSD = 4.86, P = 3.23 × 10−2), but the association was primarily driven by the TERT variant rs2736100. Serum low-density lipoprotein cholesterol and plasma HbA1C showed suggestive associations with glioma (ORSD = 1.11, P = 1.39 × 10−2 and ORSD = 1.28, P = 1.73 × 10−2, respectively), both associations being reliant on single genetic variants. Conclusions Our study provides further insight into the aetiological basis of glioma for which published data have been mixed.

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

Cited by 32 publications

References 37 publications

Associations of General and Abdominal Obesity with the Risk of Glioma Development

Associations of General and Abdominal Obesity with the Risk of Glioma Development

Associations of General and Abdominal Obesity with the Risk of Glioma Development

Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study

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