CCDC26, CDKN2BAS, RTEL1, And TERT Polymorphisms In Pediatric Brain Tumor Susceptibility

Maral ADEL FAHMIDEH, Karolinska Institutet, Sweden
TYNES T. 5 , LANNERING B. 9 , PROCHAZKA M. 1 , SCHMIDT L. 10 , GROTZER M. 6 , JOHANSEN C. 7 , KUEHNI C. 8 , LAVEBRATT C. 2 , RÖÖSLI M. 4 , SCHÜZ J. 3 , FEYCHTING M. 1

1 Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
2 Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
3 Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France
4 Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
5 The Cancer Registry of Norway, Oslo, Norway
6 Department of Oncology, University Children’s Hospital of Zurich, Zurich, Switzerland
7 Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen, Denmark
8 Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
9 Childrens Cancer Center, Queen Silvia Childrens Hospital, Gothenburg, Sweden
10 Department of Clinical Genetics, University Hospital Rigshospitalet, Copenhagen, Denmark

Purpose: 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.
Methods: 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. 
Results: The results indicated 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 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 (ptrend=0.022, ptrend=0.042, ptrend=0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (ptrend=0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (ptrend=0.009, ptrend=0.007, respectively).
Conclusions: 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.
Funding source: Swedish Council for Working Life and Social Research (2004-0504; 2007-0224), Swedish Research Council (K2008-70X-15366-04-3), Swedish Cancer Society (09 0666), Swedish Childhood Cancer Society (PROJ06/050; PROJ09/086), Swedish Radiation Protection Authority (SSI P 1572), Danish Strategic Research Council (2103-05-0006; 2064-04-0010), Swiss Federal Office of Public Health (05.001626), Swiss Research Foundation on Mobile Communication (A2006.18), Swiss National Science Foundation (PDFMP3_122873), Research Council of Norway (175163/V40).