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

doi:10.18632/oncotarget.11575

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 af dette arbejde

Institut for Klinisk Medicin

8 Citationer (Scopus)

52 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	OncoTarget
Vol/bind	7
Udgave nummer	39
Sider (fra-til)	63640-63650
Antal sider	11
ISSN	1949-2553
DOI	https://doi.org/10.18632/oncotarget.11575
Status	Udgivet - 2016

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10.18632/oncotarget.11575Licens: CC BY

Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibilityForlagets udgivne version, 3,45 MBLicens: CC BY

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Fahmideh, M. A., Lavebratt, C., Schüz, J., Röösli, M., Tynes, T., Grotzer, M. A., Johansen, C., Kuehni, C. E., Lannering, B., Prochazka, M., Schmidt, L. S., & Feychting, M. (2016). Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility. OncoTarget, 7(39), 63640-63650. https://doi.org/10.18632/oncotarget.11575

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

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.",

keywords = "Brain neoplasm, Genetic association study, Pediatric brain tumors, Single nucleotide polymorphism, Susceptibility",

author = "Fahmideh, {Maral Adel} and Catharina Lavebratt and Joachim Sch{\"u}z and Martin R{\"o}{\"o}sli and Tore Tynes and Grotzer, {Michael A.} and Christoffer Johansen and Kuehni, {Claudia E} and Birgitta Lannering and Michaela Prochazka and Schmidt, {Lisbeth Sams{\o}} and Maria Feychting",

year = "2016",

doi = "10.18632/oncotarget.11575",

language = "English",

volume = "7",

pages = "63640--63650",

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T1 - Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility

AU - Fahmideh, Maral Adel

AU - Lavebratt, Catharina

AU - Schüz, Joachim

AU - Röösli, Martin

AU - Tynes, Tore

AU - Grotzer, Michael A.

AU - Johansen, Christoffer

AU - Kuehni, Claudia E

AU - Lannering, Birgitta

AU - Prochazka, Michaela

AU - Schmidt, Lisbeth Samsø

AU - Feychting, Maria

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Brain neoplasm

KW - Genetic association study

KW - Pediatric brain tumors

KW - Single nucleotide polymorphism

KW - Susceptibility

U2 - 10.18632/oncotarget.11575

DO - 10.18632/oncotarget.11575

M3 - Journal article

C2 - 27613841

AN - SCOPUS:84994056071

SN - 1949-2553

VL - 7

SP - 63640

EP - 63650

JO - Oncotarget

JF - Oncotarget

IS - 39

ER -

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

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