DNMT3A -448A&gt;G polymorphism and cancer risk: a meta-analysis

Liu, C.H.; Tao, T.; Jiang, Liang; Xu, Bin; Zhang, Linyao; Lǚ, Kai; Zhang, X.W.; Chen, S.Q.; Liu, D.C.; Chen, M.

doi:10.4238/2015.april.17.14

Cited by 7 publications

(9 citation statements)

References 23 publications

(29 reference statements)

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“…In terms of rs1550117, our findings opposed a previous meta-analysis and we could attribute this contradiction to differences in using homozygote models (Liu et al, 2015). 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).…”

Section: Discussioncontrasting

confidence: 99%

“…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. Also, some mistakes in previous results were corrected in our study (Liu et al, 2015). At the same time, there were some limitations.…”

Section: Discussionmentioning

confidence: 59%

“…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%

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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: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 59%

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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“…However, the results from previous studies remain conflicting rather than conclusive [16, 17]. This discrepancy may be largely attributed to the insufficient sample sizes and different ethnic populations.…”

Section: Introductionmentioning

confidence: 97%

The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non-small cell lung cancer susceptibility in a Han Chinese population

Wang

Wan

et al. 2017

Oncotarget

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In this study, we conducted a case-control study to explore the association between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of rs1550117 A>G variant was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA genotype carriers. Further stratified analysis showed that rs1550117 A>G was significantly related to age (> 60 years), male, smoking and drinking. In vivo detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays consistently showed that the allele G significantly decreased DNMT3A transcription. Additional functional analysis revealed that the increased binding affinity of transcription repressor SP1, which was associated with allele G of rs1550117, led to the significant decreased expression of DNMT3A. Collectively, our results propose a suppression role of DNMT3A in NSCLC development and emphasize the dual roles of DNMT3A in tumorigenesis.

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“…GLOBOCAN estimates of cancer incidence and mortality indicate that 14.1 million new cancer cases and there were 8.2 million deaths in 2012 [1]. Cancer is a complex disease that can be affected by genetic factors [2], which can influence the susceptibility and pathophysiology of cancer [3,4]. Single nucleotide polymorphisms (SNPs) are the most common genetic variation and have become a focus in cancer research.…”

Section: Introductionmentioning

confidence: 99%