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 - on behalf of the GliomaScan consortium
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.
N1 - Funding Information:
The GICC was supported by grants from the National Institutes of Health, Bethesda, Maryland (R01CA139020, R01CA52689, P50097257, P30CA125123). Additional support was provided by the McNair Medical Institute and the Population Sciences Biorepository at Baylor College of Medicine. QTO is supported by a Research Training Grant from the Cancer Prevention and Research Institute of Texas (CPRIT; RP160097T).
Funding Information:
The UCSF Adult Glioma Study was supported by the National Institutes of Health (grant numbers R01CA52689, P50CA097257, R01CA126831, and R01CA139020), the Loglio Collective, the National Brain Tumor Foundation, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research, the Robert Magnin Newman Endowed Chair in Neuro-oncology, and by donations from families and friends of John Berardi, Helen Glaser, Elvera Olsen, Raymond E. Cooper and William Martinusen. This project also was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute‘s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention‘s National Program of Cancer Registries, under agreement # U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is neither intended nor should be inferred. Other significant contributors for the UCSF Adult Glioma Study include: M Berger, P Bracci, S Chang, J Clarke, A Molinaro, A Perry, M Pezmecki, M Prados, I Smirnov, T Tihan, K Walsh, J Wiemels, S Zheng. Glioma scan group comprised: Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Kala Visvanathan, Victoria L. Stevens, Roger Henriksson, Dominique S. Michaud, Maria Feychting, Anders Ahlbom, Graham G. Giles Roger Milne, Roberta McKean-Cowdin, Loic Le Marchand, Meir Stampfer, Avima M. Ruder, Tania Carreon, Goran Hallmans, Anne Zeleniuch-Jacquotte, J. Michael Gaziano, Howard D. Sesso, Mark P. Purdue, Emily White, Ulrike Peters, Howard D. Sesso, Julie Buring. UK10K data generation and access was organized by the UK10K consortium and funded by the Wellcome Trust. The results here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.
Funding Information:
In Sweden work was additionally supported by Acta Oncologica through the Royal Swedish Academy of Science (BM salary) and The Swedish research council and Swedish Cancer foundation. We are grateful to the National clinical brain tumor group, all clinicians and research nurses throughout Sweden who identified all cases.
Funding Information:
Key words: glioma, brain tumors, age Additional Supporting Information may be found in the online version of this article. Membership of the Gliomascan Consortium is presented in the acknowledgements. Conflict of Interest: There are no conflicts of interest to report. Grant sponsor: Cancer Prevention and Research Institute of Texas; Grant numbers: RP160097T; Grant sponsor: Centers for Disease Control and Prevention; Grant sponsor: McNair Medical Institute at Baylor College of Medicine; Grant sponsor: Population Sciences Biorepository at Baylor College of Medicine; Grant sponsor: Royal Swedish Academy of Sciences; Grant sponsor: the Loglio Collective; Grant sponsor: The National Brain Tumor Foundation; Grant sponsor: Vetenskapsrådet; Grant sponsor: Wellcome Trust; Grant sponsor: Wellcome Trust; Grant numbers: UK10K; Grant sponsor: National Cancer Institute; Grant sponsor: California Department of Public Health; Grant sponsor: California Department of Public Health; Grant sponsor: Centers for Disease Control and Prevention; Grant numbers: U58DP003862-01; Grant sponsor: Public Health Institute; Grant sponsor: University of Southern California; Grant sponsor: National Cancer Institute; Grant numbers: HHSN261201000034C HHSN261201000035C HHSN261201000140CP 30CA125123P50097257R01CA126831R01CA139020R01CA52689; Grant sponsor: California Department of Public Health; Grant sponsor: National Institutes of Health; Grant numbers: R01CA139020, R01CA126831, P50CA097257, R01CA52689, P30CA125123, P50097257; Grant sponsor: National Center for Advancing Translational Sciences; Grant sponsor: National Center for Research Resources; Grant sponsor: Swedish Cancer foundation; Grant sponsor: Swedish research council; Grant sponsor: Baylor College of Medicine DOI: 10.1002/ijc.31759 History: Received 6 Feb 2018; Accepted 16 Mar 2018; Online 27 Aug 2018 Correspondence to: Jill S. Barnholtz-Sloan, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, 11100 Euclid Ave, Cleveland, OH, 44106, E-mail: jsb42@case.edu; Tel.: 216-368-1506, Fax: 216-368-2606
Publisher Copyright:
© 2018 UICC
PY - 2018/11/15
Y1 - 2018/11/15
N2 - 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.’.
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
UR - http://www.scopus.com/inward/record.url?scp=85053534188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053534188&partnerID=8YFLogxK
U2 - 10.1002/ijc.31759
DO - 10.1002/ijc.31759
M3 - Article
C2 - 30152087
AN - SCOPUS:85053534188
VL - 143
SP - 2359
EP - 2366
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 10
ER -