Association Study of Xenobiotic Detoxication and Repair Genes with Malignant Brain Tumors in Children

Salnikova, Lyubov E.; Zelinskaya, N I; Belopolskaya, Olesya B.; Aslanyan, M. M.; Рубанович, А. В.

doi:10.32607/20758251-2010-2-4-58-65

Cited by 12 publications

(7 citation statements)

References 45 publications

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“…The expression levels of CYP1A1 are positively linked with various malignancies, such as breast, esophageal and smoking-related lung and small intestine cancer [ 22 – 26 ]. Genotyping and epidemiological studies of CYP1A1 were correlated with increased risk for brain tumor [ 27 – 29 ]. CYP1B1 is a tumor-associated protein, which has been shown to be overexpressed in various malignant tumors [ 4 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

Stavrinou¹,

Mavrogiorgou²,

Polyzoidis³

et al. 2015

PLoS ONE

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BackgroundEndogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3) and some of their proteins.MethodsUsing qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary.ResultsMeningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas.ConclusionsThe various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself.

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Section: Discussionmentioning

confidence: 99%

Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

Stavrinou¹,

Mavrogiorgou²,

Polyzoidis³

et al. 2015

PLoS ONE

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“…To our knowledge, this study represents the largest series of pediatric brain tumor cases assembled for genetic association testing to date. The association between the 29 SNPs investigated in this study and the risk of PBTs has not been examined in previous studies (8)(9)(10)(11). The SNPs were selected a priori for analyses in this study based on findings in GWAS on adult glioma, and our significant findings of associations between SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26, and risk of PBTs were consistent with findings on adult brain tumors with respect to the direction of ORs for the minor alleles (4-7).…”

Section: Discussionmentioning

confidence: 88%

“…Although large genetic studies on adult brain tumors have been conducted (3)(4)(5)(6)(7), very few and only small studies of brain tumors in children and adolescents have been reported (8)(9)(10)(11). In the last few years, four genome-wide association studies (GWAS) on adult glioma identified seven susceptibility loci at 5p15.33 (TERT), 8q24.21 (CCDC26), 9p21.3 (CDKN2A-CDKN2B), 20q13.33 (RTEL1), 11q23.3 (PHLDB1) and 7p11.2 (EGFR) (4-7).…”

Section: Introductionmentioning

confidence: 99%

CCDC26,CDKN2BAS,RTEL1andTERTPolymorphisms in pediatric brain tumor susceptibility

Fahmideh¹,

Lavebratt

Schüz

et al. 2015

CARCIN

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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. 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. The results indicated that four 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 the 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 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). 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.

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“…The PubMed database was searched (up to December 2012) using combinations of the following terms: ‘brain tumor’, ‘single nucleotide polymorphism’, ‘association’, ‘gene’, ‘risk’, ‘case control’, ‘susceptibility’, and ‘polymorphism’ to identify all the published peer-reviewed candidate gene-association studies of brain tumors. All the statistically significant SNPs reported by childhood brain tumor genetic association studies [ 11 – 13 ] as well as the SNPs reported by at least two candidate gene-association studies as being statistically associated with the risk of adult brain tumors [ 3 – 9 , 44 – 49 ] were selected for genotyping.…”

Section: Methodsmentioning

confidence: 99%

“…Whereas a considerable number of candidate gene-association studies are available on adult brain tumors, very few and small genetic studies have been performed on brain tumors in children and adolescents [ 10 – 13 ], due to difficulties in collecting a sufficient number of DNA samples. Hence, the role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Association Study of Xenobiotic Detoxication and Repair Genes with Malignant Brain Tumors in Children

Cited by 12 publications

References 45 publications

Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

CCDC26,CDKN2BAS,RTEL1andTERTPolymorphisms in pediatric brain tumor susceptibility

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

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