n.neurology.org · web view2015/09/16 · race, education, menopausal status, age at menopause,...

MS ID#: NEUROLOGY/2015/651794

ONLINE SUPPLEMENT TO:

Body mass index, physical activity, and risk of adult meningioma and glioma: a meta-

analysis

Tobias Niedermaier1, M.P.H; Gundula Behrens1, Ph.D.; Daniela Schmid1, Dr. rer. nat.; Inga

Schlecht1, M.Sc.; Beate Fischer1, Dr. oec. troph.; Michael F. Leitzmann1, M.D.

Author affiliations:

1 Department of Epidemiology and Preventive Medicine, University of Regensburg, Franz-

Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Corresponding author and reprint requests: Dr. Gundula Behrens, Department of

Epidemiology and Preventive Medicine, University of Regensburg,

Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany (email:

[email protected]; Tel.: +49-941-944-5217; Fax: +49-941-944-

5202).

1

PubMed search strategy

The PubMed search was last updated on March 1st, 2015. The following search terms were

pasted, all at once, into the PubMed search command line:

(body mass[title/abstract] OR BMI[title/abstract] OR obesity[title/abstract] OR overweight[title/abstract] OR weight[title/abstract] OR Quetelet [title/abstract] OR anthropometric[title/abstract] OR waist circumference[title/abstract] OR hip circumference[title/abstract] OR physical activity[title/abstract] OR exercis*[title/abstract] OR cardiorespiratory fitness[title/abstract] OR cardiovascular fitness[title/abstract] OR resistance training[title/abstract] OR endurance training[title/abstract] OR aerobic[title/abstract] OR sport[title/abstract] OR athletes[title/abstract] OR players[title/abstract] OR lifestyle[title/abstract] OR hormon*[title])

AND (CNS cancer[title] OR CNS cancers[title] OR brain cancer[title] OR brain cancers[title] OR glioma[title] OR gliomas[title] OR meningioma[title] OR meningiomas[title] OR cancer[title] OR cancers[title] OR neoplasm[title] OR neoplasms[title] OR malignan*[title] OR malignancies[title])

AND English[lang]

NOT (review[ptyp] OR meta-analysis[ptyp] OR editorial[ptyp] OR guideline[ptyp] OR news[ptyp])

NOT (lung*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (bronchial[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (breast*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (mamma*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (ovar*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (endometr*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (uter*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (cervi*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (gynecolog*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (prostat*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

2

NOT (testic*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (urinary*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (bladder*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (urothelial*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (colon*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (rectal*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (colorectal*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (bowel*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (*digestive*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (gastric*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (stomach*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (oesophag*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (esophag*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (pancrea*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (tract*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (duct*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (tube*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (liver*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

3

NOT (hepatocellular[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (gallbladder*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (oral*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (pharyn*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (nasopharyn*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (laryn*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (lymphoid*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (bone*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (head and neck*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (skin*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (melanoma*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (thora*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (thyroid*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (squamous cell*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (basal cell*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (adenoma*[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (multiple[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

4

NOT (mouth[title] NOT CNS cancer[title] NOT CNS cancers[title] NOT brain cancer[title] NOT brain cancers[title] NOT glioma[title] NOT gliomas[title] NOT meningioma[title] NOT meningiomas[title])

NOT (surviv*[title] OR prognosis*[title] OR quality of life*[title] OR fatigue*[title] OR pallia*[title] OR cancer patient*[title] OR cancer care*[title] OR recurrence*[title] OR progression*[title] OR clinical outcome*[title] OR chemotherapy*[title] OR radiation*[title] OR radiotherapy*[title] OR therap*[title] OR rehabilitation*[title] OR recovery*[title] OR cancer diagnosis[title] OR cancer treatment[title] OR cancer surgery[title] OR with cancer[title])

5

Figure e-1. Categorical meta-analysis of BMI and meningioma restricted to cohort studies. Forest plot of the random-effects meta-analysis of meningioma risk in relation to A) overweight (n=6 risk estimates) and B) obesity (n=7 risk estimates), stratified by definition of reference category and including information from 4 cohort studies 5,6,11,12

RR=relative risk, 95% CI=confidence interval.

6

Figure e-2. Funnel plot of overweight and meningioma meta-analysis. Funnel plot corresponding to the main random-effects meta-analysis including nine risk estimates quantifying the relationship between overweight and meningioma risk.

Figure e-3. Funnel plot of obesity and meningioma meta-analysis. Funnel plot corresponding to the main random-effects meta-analysis including 11 risk estimates quantifying the relationship between obesity and meningioma risk.

7

Figure e-4. Funnel plot of overweight and glioma meta-analysis. Funnel plot corresponding to the random-effects meta-analysis including six risk estimates quantifying the relationship between overweight and glioma risk.

Figure e-5. Funnel plot of obesity and glioma meta-analysis. Funnel plot corresponding to the random-effects meta-analysis including seven risk estimates quantifying the relationship between obesity and glioma risk.

8

Figure e-6. Funnel plot of physical activity and meningioma meta-analysis. Funnel plot corresponding to the main random-effects meta-analysis including five risk estimates quantifying the relationship between physical activity and meningioma risk.

Figure e-7. Funnel plot of physical activity and glioma meta-analysis. Funnel plot corresponding to the random-effects meta-analysis including six risk estimates quantifying the relationship between physical activity and glioma risk.

9

Table e-1: Characteristics of the 7 cohort studies and 5 case-control studies of BMI and risk of meningioma or glioma grouped by study design.

Cohort studies

Authors, years, gender

Partici-pants Cases

Maximal/averagefollow upperiod (years)

Study geographic region

Brain tumor type

Relative risk (95% CI), underweight vs. reference BMI group(if applicable)

Relative risk (95% CI), overweight vs. reference BMI group

Relative risk (95% CI), obesity vs. reference BMI group (if applicable)

Underweight BMI defined by

Reference BMI group defined by

Overweight BMI defined by

Obesity BMI defined by

Adjustment factors (excluding age and sex)

NOS score1

Benson et al., 2008 women 1,184,225 606 10/6.2 Europe meningioma Not

applicable1.01(0.79; 1.29)

1.40(1.08; 1.87)

Not applicable

BMI<25 kg/m²

BMI 25-29.9 kg/m²

BMI≥30 kg/m²

height, socioeconomic level, smoking, alcohol intake, parity, age at first birth (years), oral contraception use duration, physical activity, study region

7

358 glioma Not applicable

1.20(1.01; 1.44)

1.07(0.84; 1.34)

Edlinger et al., 2012 2

men and women combined

578,462 338 34/9.6 Europe meningioma Not applicable

1.05(0.71; 1.56)

1.39(0.96; 2.03)

Not applicable

quintile 1 (mean BMI of 21 kg/m²)



birth year (in decades), cohort, smoking status

8

98 glioma, low grade

Not applicable

1.00(0.51; 1.95)

0.66(0.31; 1.38)

410 glioma, high grade

Not applicable

1.23(0.87; 1.75)

1.14(0.80; 1.64)

8

Jhawar et al., 2003 2

women 121,700 111 21/– North America

meningioma Not applicable

1.61(0.96; 2.70)

Not applicable Not applicable

BMI<22 kg/m²

BMI≥25 kg/m²

menopausal status, postmenopausal hormone replacement therapy

6

Johnson et al., 2011 women 27,791 125 12/10.5 North

Americameningioma Not

applicable0.97(0.63; 1.52)

1.91(1.21; 3.01)for obesity class I;

1.37(0.68;2.74)for obesity classes II-III

Not applicable

BMI 18.5-24.9 kg/m²

BMI 25-29.9 kg/m²

BMI 30-34.9 kg/m² for obesity class I;

BMI ≥35 kg/m² for obesity classes II-III

None 5

10

Michaud et al., 2011 men 144,819 55 12/8.4 Europe meningioma 1.14

(0.15; 8.64)1.14(0.62; 2.12)

1.51(0.68; 3.37)

BMI<20 kg/m²

BMI 20-24.9 kg/m²

BMI 25-29.9 kg/m²

BMI≥30 kg/m²

country, education 8

women 235,689 148 meningioma 0.99(0.43; 2.33)

1.43(0.98; 2.10)

1.47(0.91; 2.36)

8


380,508 340 glioma 1.08(0.60; 1.92)

1.04(0.81; 1.34)

1.06(0.76, 1.48)

8

Moore et al., 2009 men and women combined

270,395 236 8.2/– North America

glioma 1.66(0.59; 4.64)

0.90(0.67; 1.22)

1.29(0.89; 1.86) for obesity class I;

0.74(0.37;1.48)for obesity classes II-III

BMI<18.5 kg/m²

BMI 18.5-24.9 kg/m²

BMI 25-29.9 kg/m²



race, highest level of education, marital status, physical activity, height

6

Wiedmann et al., 2013 men 36,477 30 25/23.5 Europe meningioma Not

computable because there were no cases in that group

0.88(0.41; 1.86)

0.76(0.17; 3.37)

BMI<20 kg/m²

BMI 20-24.9 kg/m²

BMI 25-29.9 kg/m²

BMI≥30 kg/m²

None 8

women 37,765 108 meningioma 0.95(0.40; 2.25)

1.37(0.87; 2.14)

1.68(0.97; 2.92)

8


74,242 148 glioma 0.67(0.29; 1.56)

0.88(0.61; 1.27)

1.04(0.58; 1.85)

8

Case-control studies

Authors, year, gender

Subjects (Cases and Controls) Cases


Brain tumor type

Relative risk (95% CI), underweight vs. reference BMI group(if applicable)

Relative risk (95% CI), overweight vs. reference BMI group

Relative risk (95% CI), obesity vs. reference BMI group (if applicable)

Underweight BMI defined by

Reference BMI group defined by

Overweight BMI defined by

Obesity BMI defined by


NOS score1

Cabaniols et al., 2011 3

11


232 116 Europe glioma Not applicable

0.70(0.41; 1.18)

Not applicable Not applicable

BMI<25 kg/m²

BMI≥25 kg/m²

None 6

Claus et al., 20132

women 2,206 1,117 North America

meningioma Not applicable

1.13(0.89; 1.45)

1.29 (1.01; 1.65)

Not applicable

BMI<23.4 kg/m²

BMI 26.6-30.9 kg/m²

BMI>30.9 kg/m²

race, education, menopausal status, age at menopause, age at menarche, number of full-term pregnancies, age at first live birth, ever use of oral contraception, ever use of hormone replacement therapy, ever use of fertility medications, smoking, alcohol use, breastfeeding

6

Custer et al., 2006 women 332 46 North

Americameningioma, expressing progesterone receptor in 0 to 25% of cells

Not applicable

1.20 (0.50; 2.50)

1.10 (0.60; 2.00)

Not applicable

BMI<25 kg/m²

BMI 25-29.9 kg/m²

BMI≥30 kg/m²

education 6

382 96 meningioma, expressing progesterone receptor in 25 to 100% of cells

1.10 (0.50; 2.40)

1.50 (0.80; 2.60)

6

Little et al., 2012 men 1,197 643 North

Americaglioma 2.47

(0.63; 9.70)1.26 (0.94; 1.69)

1.26 (0.91; 1.75)

BMI<18.5 kg/m²

BMI 18.5-24.9 kg/m²

BMI 25-29.9 kg/m²

BMI≥30 kg/m²

race, education, state of residence

4

women 1,001 460 glioma 0.80(0.34; 1.87)

0.95 (0.70; 1.29)

1.11 (0.80; 1.54)

4

Schildkraut et al., 2014 men 900 450 North

Americameningioma Not

applicable1.66 (1.17; 2.34)

1.92 (1.28; 2.90)for obesity class I;

1.64(1.02; 2.64)for obesity classes II-III

Not applicable

BMI<25 kg/m²

BMI 25-29.9 kg/m²



race 7

12

BMI=Body Mass Index.

FEV=Forced expiratory volume in one second.1NOS (Newcastle-Ottawa Scale) could take on values between 0 and 9, with 0 indicating the lowest study quality and 9 indicating the highest study quality.2Included only in a sub-analysis because non-standard definitions of the reference BMI group were used.3Included only in a sub-analysis because no separate risk estimates but a combined risk estimate were presented for overweight and obesity, defined as BMI≥25.0 kg/m².

13

Table e-2: Characteristics of the 4 cohort studies and 2 case-control studies of physical activity and risk of meningioma or glioma grouped by study design.

Cohort studies


Partici-pants Cases

Average follow up period (years)


Brain tumor type

PA domain, timing in life

Relative risk (95% CI), high vs. low PA Low PA defined by High PA defined by


NOS score1

Benson et al., 2008women 1,203,454 621 6.2 Europe glioma recreational,

recent past0.91 (0.75, 1.12) VPA less than once

per weekVPA two or more times per week

height, BMI, socioeconomic level, smoking, alcohol intake, parity, age at first birth (years), oral contraception use duration, study region

7

376 meningioma 0.73 (0.56, 0.97)

Johnson et al., 2011women 27,791 124 10.5 North

Americameningioma recreational,

recent past0.61 (0.39, 0.96) low level of PA high level of PA 5

Michaud et al., 2011men and women

380,775 316 8.4 Europe glioma total, recent past

0.95 (0.66, 1.37) quartile 1 quartile 4 country, education, BMI 7

180 meningioma 0.82 (0.50, 1.36)

Moore et al., 2009men and women

290,563 257 8.2 NorthAmerica

glioma recreational, recent past

0.86 (0.58, 1.28) ≤11.5 MET-h per week

≥51.6 MET-h per week race, highest level of education, marital status, BMI, height

6

Case-control studies


Subjects (Cases and Controls) Cases


Brain tumor type

PA domain, timing in life

Relative risk (95% CI), high vs. low PA Low PA defined by High PA defined by


NOS score1

Cabaniols et al., 2011men and women

232 116 Europe glioma recreational, recent past

1.21 (0.72, 2.03) no regular sport activity for at least 2 h per week during the 5 years prior to diagnosis/interview

regular sport activity for at least 2 h per week during the 5 years prior to diagnosis/interview

none 4

14

Preston-Martin et al., 1998men 998 349 Mixed Western

Worldglioma recreational,

recent past PA0.75 (0.60, 0.93) no sports

participation at least 5 years before diagnosis/interview

sports participation at least 5 years before diagnosis/interview

race, region 4

360 56 meningioma 0.90 (0.53, 1.52) 4

women 230 70 glioma 0.78 (0.55, 1.11) 4

166 39 meningioma 0.69 (0.45, 1.07) 4

PA=Physical Activity.

VPA=Vigorous Physical Activity.

CI=Confidence Interval.

BMI=Body Mass Index.

MET=Metabolic Equivalent of Task.

1NOS (Newcastle-Ottawa Scale) could take on values between 0 and 9, with 0 indicating the lowest study quality and 9 indicating the highest study quality.

15

Table e-3. Random effects summary estimates of meningioma and glioma risk for a high versus low level of physical activity by selected participant and design characteristics, evaluated separately for meningioma and glioma.

Stratification criterionNumber of included RRs

RRa (95% CI) p-differenceb

Brain cancer histologic type Meningioma 5 0.73 (0.61, 0.88) Glioma 6 0.86 (0.76, 0.97) 0.15

MeningiomaGender Men 1 0.90 (0.53, 1.53) Women 3 0.69 (0.56, 0.86) 0.37c

Men and women combined 1 0.82 (0.49, 1.36)Study design Cohort 3 0.72 (0.58, 0.89) Case-control 2 0.77 (0.55, 1.08) 0.73Study quality score NOS greater than or equal to 7 2 0.75 (0.59, 0.96) NOS less than 7 3 0.71 (0.54, 0.93) 0.75Adjustment for BMI Adjusted for BMI 2 0.75 (0.59, 0.96) Not adjusted for BMI 3 0.71 (0.54, 0.93) 0.75

GliomaGender Men 1 0.75 (0.60, 0.94) Women 2 0.87 (0.73, 1.05) 0.29c

Men and women combined 3 0.96 (0.76, 1.23)Study design Cohort 3 0.91 (0.77, 1.07) Case-control 3 0.80 (0.67, 0.96) 0.30Study quality score NOS greater than or equal to 7 2 0.92 (0.77, 1.10) NOS less than 7 4 0.81 (0.69, 0.95) 0.31Adjustment for BMI Adjusted for BMI 3 0.91 (0.77, 1.07) Not adjusted for BMI 3 0.80 (0.67, 0.96) 0.30RR=relative risk; CI=confidence interval; BMI=Body Mass Index.a RR comparing highest versus lowest physical activity level.b The p-difference values were obtained using meta-regression comparing the model including the stratification variable as explanatory variable with the null model not including any explanatory variables.c Comparing risk estimates of men with risk estimates of women and disregarding risk estimates of men and women combined.

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