title: MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
abstract: The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Pia
authors.initials: P
authors.lastname: Osterman
authors.forename: Sara
authors.initials: S
authors.lastname: Sjöström
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.forename: Helle
authors.initials: H
authors.lastname: Broholm
authors.forename: Helle Collatz
authors.initials: HC
authors.lastname: Christensen
authors.forename: Anders
authors.initials: A
authors.lastname: Ahlbom
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Maria
authors.initials: M
authors.lastname: Feychting
authors.forename: Stefan
authors.initials: S
authors.lastname: Lönn
authors.forename: Anne
authors.initials: A
authors.lastname: Kiuru
authors.forename: Anthony
authors.initials: A
authors.lastname: Swerdlow
authors.forename: Minouk
authors.initials: M
authors.lastname: Schoemaker
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Beatrice
authors.initials: B
authors.lastname: Malmer
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000628:therapy; D008579:Meningioma / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D011379:Prognosis; D019098:Telomerase / Q000235:genetics; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase