Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

Maral Adel Fahmideh*, Catharina Lavebratt, Joachim Schüz, Martin Röösli, Tore Tynes, Michael A. Grotzer, Christoffer Johansen, Claudia E Kuehni, Birgitta Lannering, Michaela Prochazka, Lisbeth Samsø Schmidt, Maria Feychting

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
JournalOncoTarget
Volume7
Issue number39
Pages (from-to)63640-63650
Number of pages11
ISSN1949-2553
DOIs
Publication statusPublished - 2016

Keywords

  • Brain neoplasm
  • Genetic association study
  • Pediatric brain tumors
  • Single nucleotide polymorphism
  • Susceptibility

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