title: CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility.
abstract: The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways.
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden, Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm SE-171 76, Sweden, Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel 4002, Switzerland, University of Basel, Basel 4003, Switzerland, The Cancer Registry of Norway, Oslo N-0304, Norway, National Institute of Occupational Health, Oslo NO-0033, Norway, Department of Oncology, University Children's Hospital of Zurich, Zurich 8091, Switzerland, Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen DK-2100, Denmark, 5073 Oncology Clinic, Finsen Centre Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark, Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern 3012, Switzerland, Department of Clinical Sciences, Pediatric Oncology, University of Gothenburg, SE 416 85 Gothenburg, Sweden and Department of Pediatric Oncology, University Hospital Rigshospitalet, Copenhagen DK-2100, Denmark maral.adel.fahmideh@ki.se.
authors.forename: Maral
authors.initials: M
authors.lastname: Adel Fahmideh
authors.affiliation: Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm SE-171 76, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.affiliation: Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Schüz
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel 4002, Switzerland, University of Basel, Basel 4003, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Röösli
authors.affiliation: The Cancer Registry of Norway, Oslo N-0304, Norway, National Institute of Occupational Health, Oslo NO-0033, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Tynes
authors.affiliation: Department of Oncology, University Children's Hospital of Zurich, Zurich 8091, Switzerland.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grotzer
authors.affiliation: Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen DK-2100, Denmark, 5073 Oncology Clinic, Finsen Centre Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern 3012, Switzerland.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Kuehni
authors.affiliation: Department of Clinical Sciences, Pediatric Oncology, University of Gothenburg, SE 416 85 Gothenburg, Sweden and.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lannering
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden, Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm SE-171 76, Sweden, Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel 4002, Switzerland, University of Basel, Basel 4003, Switzerland, The Cancer Registry of Norway, Oslo N-0304, Norway, National Institute of Occupational Health, Oslo NO-0033, Norway, Department of Oncology, University Children's Hospital of Zurich, Zurich 8091, Switzerland, Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen DK-2100, Denmark, 5073 Oncology Clinic, Finsen Centre Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark, Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern 3012, Switzerland, Department of Clinical Sciences, Pediatric Oncology, University of Gothenburg, SE 416 85 Gothenburg, Sweden and Department of Pediatric Oncology, University Hospital Rigshospitalet, Copenhagen DK-2100, Denmark.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prochazka
authors.affiliation: Department of Pediatric Oncology, University Hospital Rigshospitalet, Copenhagen DK-2100, Denmark.
authors.forename: Lisbeth S
authors.initials: LS
authors.lastname: Schmidt
authors.affiliation: Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden, Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm SE-171 76, Sweden, Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel 4002, Switzerland, University of Basel, Basel 4003, Switzerland, The Cancer Registry of Norway, Oslo N-0304, Norway, National Institute of Occupational Health, Oslo NO-0033, Norway, Department of Oncology, University Children's Hospital of Zurich, Zurich 8091, Switzerland, Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen DK-2100, Denmark, 5073 Oncology Clinic, Finsen Centre Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark, Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern 3012, Switzerland, Department of Clinical Sciences, Pediatric Oncology, University of Gothenburg, SE 416 85 Gothenburg, Sweden and Department of Pediatric Oncology, University Hospital Rigshospitalet, Copenhagen DK-2100, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Feychting
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D004265:DNA Helicases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005910:Glioma / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D062085:RNA, Long Noncoding; C000613877:long noncoding RNA CCDC26, human; C509186:TERT protein, human; D019098:Telomerase; C532890:RTEL1 protein, human; D004265:DNA Helicases