Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer

Wang, Chuan; Jia, Zhifang; Cao, Donghui; You, Lili; Jin, Meishan; Wu, Xing; Wen, Simin; Cao, Xueyuan; Jiang, Jing

doi:10.1371/journal.pone.0134059

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…Then 25 full-text articles were obtained to be assessed, in which 5 articles were excluded because 1 was duplicate publication and 4 did not contain information on DNMTs SNPs and GC risk. Ultimately, 20 eligible studies (Jiang et al, 2012a, Yang et al, 2012, Yan et al, 2015, Khatami et al, 2009, Wu et al, 2014, Cao et al, 2013, Wu et al, 2012, Fan et al, 2010, Liu, 2009, Zhang et al, 2014, Hu et al, 2010, Zhang, 2008, Liu, 2008, Wang et al, 2005, Aung et al, 2005, Wang et al, 2015a, Jiang et al, 2013, Jiang et al, 2012b, Cao et al, 2012, Chang et al, 2010)were included in the qualitative synthesis, and 7 of them could not be quantitatively synthesized (3 studies respectively reported a different SNP (Wu et al, 2014, Wu et al, 2012, Liu, 2008), 4 studies were conference abstracts (Jiang et al, 2013, Jiang et al, 2012b, Cao et al, 2012, Chang et al, 2010)), so 13 studies involving 3959 GC cases and 5992 healthy controls were finally included in the meta-analysis (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…For rs1569686, we consider it as a protective factor for gastric carcinogenesis and similar results were discovered in head and neck cancer, lung cancer and colorectal cancer (Duan et al, 2015, Zhang et al, 2015, Xia et al, 2015, Zhu et al, 2012). However, another study argued it was associated with poor prognosis in GC cases (Wang et al, 2015a). Maybe it played different roles in pathogenesis and prognosis.…”

Section: Discussionmentioning

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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

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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“…Subjects of the study were described elsewhere [ 24 , 25 ]. From August 2008 to December 2010, a total of 447 GC patients who underwent tumorectomy in the Department of Gastric and Colorectal Surgery of the First Hospital of Jilin University were recruited in this study.…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

Jia

Cao

et al. 2016

Disease Markers

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DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, P = 0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, P = 0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.

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“…Until 2015, the incidence of gastric cancer has increased on a yearly basis and two thirds of all new cases were reported in developing countries, among which China accounted for 42% (3). As patients with gastric cancer are typically asymptomatic during the early stage of the disease, early diagnosis of gastric cancer is difficult and the five-year survival rate of all patients with gastric cancer is <20% (4).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11

Yang

Mei

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to evaluate the expression of microRNA (miR)-421 in gastric cancer and to investigate its biological function and underlying mechanism of action in the development of gastric cancer. The expression of miR-421 was measured in 60 pairs of clinically removed gastric cancer tissues and matched adjacent normal gastric tissues by reverse transcription-quantitative polymerase chain reaction. In addition, following transfection with an miR-421 inhibitor to suppress the expression of miR-421, the proliferation, migration and cell cycle distribution of human gastric carcinoma MKN28/MKN74 cells were determined by cell counting, Transwell and flow cytometry assays. The target gene of miR-421 was also predicted using bioinformatic analysis and verified by dual-luciferase reporter gene assay and western blot analysis. Furthermore, overexpression of the miR-421 target protein was induced in MKN28/MKN74 cells to determine its function. It was observed that miR-421 was significantly upregulated in gastric cancer tissues and that the expression of miR-421 was associated with lymph node metastasis and the clinical stage of gastric cancer (all P<0.05). Claudin11 (CLDN11) was predicted and verified as a direct target of miR-421. In vitro experiments demonstrated that inhibition of miR-421 expression suppressed the proliferation and metastasis of MKN28/MKN74 cells and induced G1/S-phase cell cycle arrest (all P<0.05). Analagous results were observed in MKN28/MKN74 cells following overexpression of the CLDN11 protein. Collectively, these data suggest that miR-421 may promote the proliferation, invasion and metastasis of gastric cancer by inhibiting the expression of CLDN11.

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Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer

Cited by 13 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

Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

MicroRNA-421 promotes the proliferation and metastasis of gastric cancer cells by targeting claudin-11

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