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dc.contributor.authorOstrom, QT
dc.contributor.authorKinnersley, B
dc.contributor.authorArmstrong, G
dc.contributor.authorRice, T
dc.contributor.authorChen, Y
dc.contributor.authorWiencke, JK
dc.contributor.authorMcCoy, LS
dc.contributor.authorHansen, HM
dc.contributor.authorAmos, CI
dc.contributor.authorBernstein, JL
dc.contributor.authorClaus, EB
dc.contributor.authorEckel-Passow, JE
dc.contributor.authorIl'yasova, D
dc.contributor.authorJohansen, C
dc.contributor.authorLachance, DH
dc.contributor.authorLai, RK
dc.contributor.authorMerrell, RT
dc.contributor.authorOlson, SH
dc.contributor.authorSadetzki, S
dc.contributor.authorSchildkraut, JM
dc.contributor.authorShete, S
dc.contributor.authorRubin, JB
dc.contributor.authorAndersson, U
dc.contributor.authorRajaraman, P
dc.contributor.authorChanock, SJ
dc.contributor.authorLinet, MS
dc.contributor.authorWang, Z
dc.contributor.authorYeager, M
dc.contributor.authorGliomaScan consortium,
dc.contributor.authorHoulston, RS
dc.contributor.authorJenkins, RB
dc.contributor.authorWrensch, MR
dc.contributor.authorMelin, B
dc.contributor.authorBondy, ML
dc.contributor.authorBarnholtz-Sloan, JS
dc.date.accessioned2018-09-13T10:07:53Z
dc.date.issued2018-11-15
dc.identifier.citationInternational journal of cancer, 2018, 143 (10), pp. 2359 - 2366
dc.identifier.issn0020-7136
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2681
dc.identifier.eissn1097-0215
dc.identifier.doi10.1002/ijc.31759
dc.description.abstractGlioblastoma (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 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 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 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 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.'
dc.formatPrint-Electronic
dc.format.extent2359 - 2366
dc.languageeng
dc.language.isoeng
dc.publisherWILEY
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectGliomaScan consortium
dc.subjectHumans
dc.subjectGlioblastoma
dc.subjectBrain Neoplasms
dc.subjectCase-Control Studies
dc.subjectAge Factors
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectYoung Adult
dc.subjectNeoplasm Grading
dc.titleAge-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age.
dc.typeJournal Article
dcterms.dateAccepted2018-03-16
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1002/ijc.31759
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of cancer
pubs.issue10
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.volume143
pubs.embargo.termsNot known
icr.researchteamCancer Genomics
dc.contributor.icrauthorKinnersley, Benjamin
dc.contributor.icrauthorHoulston, Richard


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