Polymorphism of DNA methyltransferase 3B −149C/T and cancer risk: a meta-analysis

Zhu, Jing; Du, Songtao; Zhang, Jiaqi; Wang, Yingnan; Wu, Qiaoling; Ni, Jixiang

doi:10.1007/s12032-014-0399-4

Cited by 16 publications

(9 citation statements)

References 34 publications

(22 reference statements)

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“…Previous meta-analysis studies primarily evaluated associations between a few SNPs and cancers without classification, such as GC (Zhu et al, 2015, Duan et al, 2015, Liu et al, 2015, Zhang et al, 2015, Xia et al, 2015). The major strengths of our study was its comprehensive and systematic focus on GC and SNPs from three main types of DNMTs , 17 SNPs in total.…”

Section: Discussionmentioning

confidence: 99%

“…There is considerable evidence that a number of abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs ( DNMT1 , DNMT3A and DNMT3B ), which could cause DNA hypo-methylation or hyper-methylation (Gao et al, 2011, Fu et al, 2010, Harder et al, 2008, Zhao and Bu, 2012), are correlated to tumor occurrence or decrease (Luo et al, 2015, Chang et al, 2014, Mostowska et al, 2013, Kullmann et al, 2013, Sun et al, 2012, Xiang et al, 2010, Kanai et al, 2003) such as head and neck cancer, and colorectal cancer (Zhu et al, 2015, Duan et al, 2015). However, the associations between DNMTs SNPs and GC risk were still conflicting (Jiang et al, 2012a, Yang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Liu

et al. 2016

EBioMedicine

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BackgroundIncreasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC.MethodsFirstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review.Findings20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14–1.61; dominant model: OR 1.36, 95%CI 1.15–1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38–3.00; dominant model: OR 1.20, 95%CI 1.01–1.42; recessive model: OR 1.96, 95%CI 1.33–2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61–0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.48, 95%CI 0.36–0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.49, 95%CI 0.37–0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation.ConclusionThis meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Liu

et al. 2016

EBioMedicine

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“…In the present study, we observed that DNMT3B T carrier genotypes (CT and TT) may offer a protective effect against AML development, while SLC19A1 G carrier genotypes (AG and GG) increased the risk of this malignancy. Although, the association of DNMT3B variants with cancer susceptibility has been reported in the literature , it remains unclear . To our best knowledge, only one report studied the association of DNMT3B gene with hematological neoplasias , finding that C allele could confer a protective effect against AML development in Chinese Han population.…”

Section: Discussionmentioning

confidence: 98%

Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis

et al. 2016

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Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

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“…Many studies have described the association of two common polymorphisms rs1569686 (-579G>T) and rs2424913 (-149C>T) on the promoter of DNMT3B which alter the promoter activity [138][139]. However, there is conflicting evidence on the contribution of these two SNPs in different cancers [140][141][142][143].…”

Section: Polymorphisms In Dnmts and Gastric Cancer Developmentmentioning

confidence: 99%

DNA Methyltransferases and Gastric Cancer: Insight Into Targeted Therapy

et al. 2018

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Gastric cancer is a major health problem worldwide occupying most frequent causes of cancerrelated mortality. In addition to genetic modifications, epigenetic alterations catalyzed by DNA methyltransferases (DNMTs) is a well-characterized epigenetic hallmark in gastric cancer. The reversible nature of epigenetic alterations and central role of DNA methylation in diverse biological processes provides an opportunity for using DNA methyltransferase inhibitors to enhance the efficacy of chemotherapeutics. In this review, we discussed key factors or mechanisms such as SNPs, infections, and genetic modifications that trigger DNMTs level modification in gastric cancer, and their potential roles in cancer progression. Finally, we focused on how inhibitors of the DNMTs can most effectively be used for the treatment of gastric cancer with multidrug resistance.

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Polymorphism of DNA methyltransferase 3B −149C/T and cancer risk: a meta-analysis

Cited by 16 publications

References 34 publications

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

DNMT1 , DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis

Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis

DNA Methyltransferases and Gastric Cancer: Insight Into Targeted Therapy

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