Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility.
Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk.The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression.The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratified analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected.This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Maral
M
Adel Fahmideh
Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, L8:00, SE-171 76 Stockholm, Sweden.
Catharina
C
Lavebratt
Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 69372 Lyon, France.
Joachim
J
Schüz
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.|University of Basel, 4003 Basel, Switzerland.
Martin
M
Röösli
The Cancer Registry of Norway, NO-0379 Oslo, Norway.|National Institute of Occupational Health, NO-0360 Oslo, Norway.
Tore
T
Tynes
Department of Oncology, University Children's Hospital of Zurich, 8032 Zurich, Switzerland.
Michael A
MA
Grotzer
Unit of Survivorship, The Danish Cancer Society Research Centre, DK-2100 Copenhagen, Denmark.|Oncology Department, Finsen Centre, Rigshospitalet, DK-2100 Copenhagen, Denmark.
Christoffer
C
Johansen
Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, 3012 Bern, Switzerland.
Claudia E
CE
Kuehni
Childrens Cancer Center, Queen Silvia Childrens Hospital, SE-416 85 Gothenburg, Sweden.
Birgitta
B
Lannering
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Michaela
M
Prochazka
Department of Clinical Genetics, University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark.
Lisbeth S
LS
Schmidt
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Maria
M
Feychting
D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D004260:DNA Repair; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012306:Risk; D012463:Saliva / Q000378:metabolism; D013548:Sweden; D013557:Switzerland; D055815:Young Adult
D018797:Cell Cycle Proteins
brain neoplasm; genetic association study; pediatric brain tumors; single nucleotide polymorphism; susceptibility