dc.contributor.author | Ostrom, QT | |
dc.contributor.author | Kinnersley, B | |
dc.contributor.author | Armstrong, G | |
dc.contributor.author | Rice, T | |
dc.contributor.author | Chen, Y | |
dc.contributor.author | Wiencke, JK | |
dc.contributor.author | McCoy, LS | |
dc.contributor.author | Hansen, HM | |
dc.contributor.author | Amos, CI | |
dc.contributor.author | Bernstein, JL | |
dc.contributor.author | Claus, EB | |
dc.contributor.author | Eckel-Passow, JE | |
dc.contributor.author | Il'yasova, D | |
dc.contributor.author | Johansen, C | |
dc.contributor.author | Lachance, DH | |
dc.contributor.author | Lai, RK | |
dc.contributor.author | Merrell, RT | |
dc.contributor.author | Olson, SH | |
dc.contributor.author | Sadetzki, S | |
dc.contributor.author | Schildkraut, JM | |
dc.contributor.author | Shete, S | |
dc.contributor.author | Rubin, JB | |
dc.contributor.author | Andersson, U | |
dc.contributor.author | Rajaraman, P | |
dc.contributor.author | Chanock, SJ | |
dc.contributor.author | Linet, MS | |
dc.contributor.author | Wang, Z | |
dc.contributor.author | Yeager, M | |
dc.contributor.author | GliomaScan consortium, | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Jenkins, RB | |
dc.contributor.author | Wrensch, MR | |
dc.contributor.author | Melin, B | |
dc.contributor.author | Bondy, ML | |
dc.contributor.author | Barnholtz-Sloan, JS | |
dc.date.accessioned | 2018-09-13T10:07:53Z | |
dc.date.issued | 2018-11-15 | |
dc.identifier.citation | International journal of cancer, 2018, 143 (10), pp. 2359 - 2366 | |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2681 | |
dc.identifier.eissn | 1097-0215 | |
dc.identifier.doi | 10.1002/ijc.31759 | |
dc.description.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 [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.format | Print-Electronic | |
dc.format.extent | 2359 - 2366 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | GliomaScan consortium | |
dc.subject | Humans | |
dc.subject | Glioblastoma | |
dc.subject | Brain Neoplasms | |
dc.subject | Case-Control Studies | |
dc.subject | Age Factors | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Young Adult | |
dc.subject | Neoplasm Grading | |
dc.title | Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-03-16 | |
rioxxterms.funder | The Institute of Cancer Research | |
rioxxterms.identifier.project | Unspecified | |
rioxxterms.versionofrecord | 10.1002/ijc.31759 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of cancer | |
pubs.issue | 10 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 143 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Kinnersley, Benjamin | |
dc.contributor.icrauthor | Houlston, Richard | |