Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
Author: Adel Fahmideh, Maral; Lavebratt, Catharina; Schüz, Joachim; Röösli, Martin; Tynes, Tore; Grotzer, Michael A; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Prochazka, Michaela; Schmidt, Lisbeth S; Feychting, Maria
Department: Institutet för miljömedicin / Institute of Environmental Medicine
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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, stratifid 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.
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, stratifid 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.
Institution:
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Cancer Registry of Norway, Oslo, Norway
- National Institute of Occupational Health, Oslo, Norway
- Department of Oncology, University Children’s Hospital of Zurich, Zurich, Switzerland
- Unit of Survivorship, The Danish Cancer Society Research Centre, Copenhagen, Denmark
- Oncology Department, Finsen Centre, Rigshospitalet, Copenhagen, Denmark
- Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- Childrens Cancer Center, Queen Silvia Childrens Hospital, Gothenburg, Sweden
- Department of Clinical Genetics, University Hospital Rigshospitalet, Copenhagen, Denmark
- Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
Citation: Oncotarget. 2016 Sep 27;7(39):63640-63650.
Citation DOI: 10.18632/oncotarget.11575
Citation PMID: 27613841
Citation ISI: 000387167800064
Publishing journal: Oncotarget
Eprint status: Peer Reviewed
Version: Published
Issue date: 2016-10-05
Sponsorship:
- 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 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
- Swedish Childhood Cancer Society, PROJ06/050, PROJ09/086
Rights:
CC BY 4.0
Publication year: 2016
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