Age-specific genome-wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’-like features associated with younger age

on behalf of the GliomaScan consortium

doi:10.1002/ijc.31759

Age-specific genome-wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’-like features associated with younger age

on behalf of the GliomaScan consortium

Institut for Klinisk Medicin

7 Citationer (Scopus)

Abstract

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p _54–63 = 1.50x10 ⁻⁹ , OR _54–63 = 1.28, 95%CI _54–63 = 1.18–1.39; p ₆₄₊ = 2.14x10 ⁻¹¹ , OR ₆₄₊ = 1.32, 95%CI ₆₄₊ = 1.21–1.43] and rs11979158 [p _54–63 = 6.13x10 ⁻⁸ , OR _54–63 = 1.35, 95%CI _54–63 = 1.21–1.50; p ₆₄₊ = 2.18x10 ⁻¹⁰ , OR ₆₄₊ = 1.42, 95%CI ₆₄₊ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p _18–53 = 9.30 × 10 ⁻¹¹ , OR _18–53 = 1.76, 95%CI _18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’-like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’.

Originalsprog	Engelsk
Tidsskrift	International Journal of Cancer
Vol/bind	143
Udgave nummer	10
Sider (fra-til)	2359-2366
Antal sider	8
ISSN	0020-7136
DOI	https://doi.org/10.1002/ijc.31759
Status	Udgivet - 2018

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10.1002/ijc.31759

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205887/Licens: Andet

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@article{82085c41ac7847a39946ecc5abff5864,

title = "Age-specific genome-wide association study in glioblastoma identifies increased proportion of {\textquoteleft}lower grade glioma{\textquoteright}-like features associated with younger age",

abstract = " Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p 54–63 = 1.50x10 −9 , OR 54–63 = 1.28, 95%CI 54–63 = 1.18–1.39; p 64+ = 2.14x10 −11 , OR 64+ = 1.32, 95%CI 64+ = 1.21–1.43] and rs11979158 [p 54–63 = 6.13x10 −8 , OR 54–63 = 1.35, 95%CI 54–63 = 1.21–1.50; p 64+ = 2.18x10 −10 , OR 64+ = 1.42, 95%CI 64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p 18–53 = 9.30 × 10 −11 , OR 18–53 = 1.76, 95%CI 18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of {\textquoteleft}LGG{\textquoteright}-like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with {\textquoteleft}secondary glioblastoma.{\textquoteright}. ",

keywords = "age, brain tumors, glioma",

author = "Ostrom, {Quinn T.} and Ben Kinnersley and Georgina Armstrong and Terri Rice and Yanwen Chen and Wiencke, {John K.} and McCoy, {Lucie S.} and Hansen, {Helen M.} and Amos, {Christopher I.} and Bernstein, {Jonine L.} and Claus, {Elizabeth B.} and Eckel-Passow, {Jeanette E.} and Dora Il'yasova and Christoffer Johansen and Lachance, {Daniel H.} and Lai, {Rose K.} and Merrell, {Ryan T.} and Olson, {Sara H.} and Siegal Sadetzki and Schildkraut, {Joellen M.} and Sanjay Shete and Rubin, {Joshua B.} and Ulrika Andersson and Preetha Rajaraman and Chanock, {Stephen J.} and Linet, {Martha S.} and Zhaoming Wang and Meredith Yeager and Houlston, {Richard S.} and Jenkins, {Robert B.} and Wrensch, {Margaret R.} and Beatrice Melin and Bondy, {Melissa L.} and Barnholtz-Sloan, {Jill S.} and {on behalf of the GliomaScan consortium}",

year = "2018",

doi = "10.1002/ijc.31759",

language = "English",

volume = "143",

pages = "2359--2366",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "10",

}

TY - JOUR

T1 - Age-specific genome-wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’-like features associated with younger age

AU - Ostrom, Quinn T.

AU - Kinnersley, Ben

AU - Armstrong, Georgina

AU - Rice, Terri

AU - Chen, Yanwen

AU - Wiencke, John K.

AU - McCoy, Lucie S.

AU - Hansen, Helen M.

AU - Amos, Christopher I.

AU - Bernstein, Jonine L.

AU - Claus, Elizabeth B.

AU - Eckel-Passow, Jeanette E.

AU - Il'yasova, Dora

AU - Johansen, Christoffer

AU - Lachance, Daniel H.

AU - Lai, Rose K.

AU - Merrell, Ryan T.

AU - Olson, Sara H.

AU - Sadetzki, Siegal

AU - Schildkraut, Joellen M.

AU - Shete, Sanjay

AU - Rubin, Joshua B.

AU - Andersson, Ulrika

AU - Rajaraman, Preetha

AU - Chanock, Stephen J.

AU - Linet, Martha S.

AU - Wang, Zhaoming

AU - Yeager, Meredith

AU - Houlston, Richard S.

AU - Jenkins, Robert B.

AU - Wrensch, Margaret R.

AU - Melin, Beatrice

AU - Bondy, Melissa L.

AU - Barnholtz-Sloan, Jill S.

AU - on behalf of the GliomaScan consortium

PY - 2018

Y1 - 2018

N2 - Glioblastoma 54–63 = 1.50x10 −9 , OR 54–63 = 1.28, 95%CI 54–63 = 1.18–1.39; p 64+ = 2.14x10 −11 , OR 64+ = 1.32, 95%CI 64+ = 1.21–1.43] 54–63 = 6.13x10 −8 , OR 54–63 = 1.35, 95%CI 54–63 = 1.21–1.50; p 64+ = 2.18x10 −10 , OR 64+ = 1.42, 95%CI 64+ = 1.27–1.58]) 18–53 = 9.30 × 10 −11 , OR 18–53 = 1.76, 95%CI 18–53 = 1.49–2.10). (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p and rs11979158 [p but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’-like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’.

AB - Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p 54–63 = 1.50x10 −9 , OR 54–63 = 1.28, 95%CI 54–63 = 1.18–1.39; p 64+ = 2.14x10 −11 , OR 64+ = 1.32, 95%CI 64+ = 1.21–1.43] and rs11979158 [p 54–63 = 6.13x10 −8 , OR 54–63 = 1.35, 95%CI 54–63 = 1.21–1.50; p 64+ = 2.18x10 −10 , OR 64+ = 1.42, 95%CI 64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p 18–53 = 9.30 × 10 −11 , OR 18–53 = 1.76, 95%CI 18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’-like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’.

KW - age

KW - brain tumors

KW - glioma

U2 - 10.1002/ijc.31759

DO - 10.1002/ijc.31759

M3 - Journal article

C2 - 30152087

AN - SCOPUS:85053534188

SN - 0020-7136

VL - 143

SP - 2359

EP - 2366

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 10

ER -

Age-specific genome-wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’-like features associated with younger age

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