Functional Polymorphisms in Folate Metabolism Genes Influence the Risk of Meningioma and Glioma

Bethke, Lara; Webb, Emily L.; Murray, Anne R.; Schoemaker, Minouk J.; Feychting, Maria; Lönn, Stefan; Ahlbom, Anders; Malmer, Beatrice; Henriksson, Roger; Auvinen, Anssi; Kiuru, Anne; Salminen, Tiina; Johansen, Christoffer; Christensen, Helle Collatz; Muir, Kenneth; McKinney, Patricia A.; Hepworth, Sarah; Dimitropoulou, Polyxeni; Lophatananon, Artitaya; Swerdlow, Anthony; Houlston, Richard S.

doi:10.1158/1055-9965.epi-07-2733

Cited by 51 publications

(54 citation statements)

References 23 publications

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“…For A1298C, only heterozygous genes were associated with the risk of glioma. Although single nucleotide polymorphisms have regional differences, our findings are nonetheless consistent with Bethke et al (2008). Only a few studies have investigated polymorphisms of MTHFR in brain tumors to date.…”

Section: Discussionsupporting

confidence: 86%

“…With respect to the relationship between polymorphisms and protein activity of MTH-FR, previous studies have found that homozygotes and wild type genotypes for both C677T and A1298C lead to changes in protein activity (Frosst et al, 1995;Bethke et al, 2008). Our results demonstrated that only patients who were heterozygous for C677T showed the highest rates of MGMT methylation, whereas those who were heterozygous for A1298C did not.…”

Section: Discussionsupporting

confidence: 48%

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Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels

Liu¹,

Jiang²,

Song³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Hypomethylation of the O6-methylguanine-DNAmethyltransferase (MGMT) promoter in glioma cells has been associated with temozolomide resistance. S-adenosylmethionine (SAM), which is produced during folate metabolism, is the main source of methyl groups during DNA methylation. As a key enzyme during folate metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may regulate folate end-products. We investigated the effect of typical polymorphisms of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate levels in patients with glioma from Northeast China. A total of 275 patients with glioma and 329 without malignant MTHFR polymorphisms and MGMT methylation tumors were tested. Serum folate concentration was assayed by using the electrochemiluminescence immunoassay. MTHFR polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The constituent ratio of glioma patients below the serum folate biological reference value was significantly higher than that of the control population (P < 0.001). In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C mutation were found in higher frequency than homozygotes or wild types (oligodendroglioma, P < 0.001; glioblastoma, P < 0.01). When grouped by the median or biological reference value of serum folate, only homozygotes for C677T with low levels of folate were significantly associated with decreased methylation of MGMT (median, P < 0.001; biological reference value, P = 0.036). These data suggest that, in combination with a negative folate balance in glioma patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 48%

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels

Liu¹,

Jiang²,

Song³

et al. 2013

Genet. Mol. Res.

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“…Our review indicated that currently available studies do not provide enough supportive information to establish genes involved in metabolism for PBT risk assessment (Table 3 [71][72][73][74][75][76][77][78][79][80][81][82][83] ). Contradictory results were observed for MTHFR, MTRR, NAT2, and PON1 for glioma.…”

Section: Pbts Molecular Epidemiologic Studies With Focus On Metabolismmentioning

confidence: 99%

Molecular Epidemiology of Primary Brain Tumors

Liu

Kyritsis

et al. 2009

Neurotherapeutics

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Summary:Although primary brain tumors (PBTs) are generally considered to be a multifactorial disorder, understanding the genetic basis and etiology of the disease is essential for PBT risk assessment. Understanding of the genetic susceptibility for PBT has come from studies of rare genetic syndromes, linkage analysis, family aggregation, early-onset pediatric cases, and mutagen sensitivity. There are currently no effective markers to assess biological dose of exposures and genetic heterogeneity. The priorities recently recommended by the Brain Tumor Epidemiology Consortium emphasized the need for expanding research in genetics and molecular epidemiology. In this article, we review the literature to identify molecular epidemiologic case-control studies of PBTs that were hypothesis-driven and focused on four hypothesized candidate pathways: DNA repair, cell cycle, metabolism, and inflammation. We summarize the results in terms of genetic associations of single nucleotide polymorphisms of these pathways. We also discuss future research directions based on available evidence and technologies, and conclude that high resolution whole genome approach with significantly large sample size could rapidly advance our understanding of the genetic etiology of PBTs. Literature searches were done on PubMed in March 2009 with the terms glioma, glioblastoma, brain tumor, association, and polymorphism, and we only reviewed English language publications.

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“…When compared to controls with the cc genotype, patients with the TT genotype showed an increased risk, with an or of 2.92 (adjusted for age, gender and smoking status) and 95% ci 1.14-7.47. (18)(19)(20). The association between carcinogenesis and the AXIN2 polymorpism was recently investigated in a few populations (21-23).…”

Section: Characteristics Of Primary Brain Tumor Patients and Healthymentioning

confidence: 99%

AXIN2 polymorphism and its association with astrocytoma in a Turkish population

Gunes

Pınarbaşı²,

Pınarbaşı³

2010

Mol Med Rep

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Abstract. The product of AXIN2, a component of Wnt signalling, plays a role in tumorigenesis and is dysregulated in cancer cells. in order to determine whether the AXIN2 polymorphism is a risk factor for astrocytoma, we analysed eight polymorphic regions of this gene in 100 astrocytoma patients compared to 100 healthy controls in a Turkish population using Pcr-rFlP methods. For the exon1-148 T/c, exon1-432 c/T, exon5-1365 G/a, intron5-1712+19G/T, exon7-2062 c/T and intron7-2141+73 G/a SnPs of AXIN2, no significant association between controls and astrocytoma patients was found. For the exon5-1386 c/T SnP, a statistically significant association between controls and patients was found (p<0.05). For this astrocytoma, patients with the TT genotype showed an increased risk with an or of 2.92 (adjusted for age, gender and smoking status) (95% ci 1.14-7.47) as compared to the controls with the cc genotype. our results suggest that AXIN2 SNPs may be associated with astrocytoma.

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Functional Polymorphisms in Folate Metabolism Genes Influence the Risk of Meningioma and Glioma

Cited by 51 publications

References 23 publications

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels

Molecular Epidemiology of Primary Brain Tumors

AXIN2 polymorphism and its association with astrocytoma in a Turkish population

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