Gene expression and promoter polymorphisms of DNA methyltransferase 3B in nasopharyngeal carcinomas in Taiwanese people: A case-control study

Chang, Kai‐Ping; Hao, Sheng‐Po; Tsang, Ngan‐Ming; Chang, Yu‐Cheng; Cheng, Ming‐Huei; Liu, Chun‐Ting; Lee, Yun‐Shien; Tsai, Chia-Lung; Lee, Ta‐Jen; Wang, Tzu‐Hao; Tsai, Chun‐Yi

doi:10.3892/or.19.1.217

Cited by 9 publications

(9 citation statements)

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“…However, the role of rs2424913 on cancer in Chinese could be negligible as the C allele in Chinese population is absent or rare [ 20 ], the significance of great diversity in DNMT3b SNP distribution may be due to different ethnic groups, unknown environmental factors or the interplay between environmental factors and genetic predisposition. The rs1569686 was reported to be associated with the susceptibility of lung cancer [ 31 ] and gastric cancer [ 21 ] but not in hepatocellular carcinoma [ 19 ], esophagus cancer [ 32 ] and nasopharyngeal carcinoma [ 20 ]. In a previous meta-analysis based on 24 case-control studies, the DNMT3b rs1569686 G allele has been identified as a low risk factor for developing colorectal cancer [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…It was considered that single nucleotide polymorphisms (SNPs) within the promoter region of DNMT3b gene may modify gene expression levels [ 18 ]. Previous studies have shown that SNPs of DNMT3b were correlated with the susceptibility of various cancers, such as hepatocellular carcinoma [ 19 ], lung cancer [ 18 ], nasopharyngeal carcinomas [ 20 ], breast cancer [ 7 ] and gastric cancer [ 21 ], and Azad et al [ 22 ] have demonstrated that DNMT3b rs2424913 polymorphism was correlated with an increased hazard risk of in head and neck cancer. These SNPs were found to affect the activity of DNMT3b on DNA methylation by changing the level of DNMT3b, thereby modulating the susceptibility to cancer [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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ObjectiveDNA methyltransferase 3b (DNMT3b) plays an important role in abnormal methylation during tumorigenesis. Polymorphism of the DNMT3b gene may influence DNMT3b activity and be associated with cancer risk. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the DNMT3b gene and susceptibility and prognosis of gastric cancer.MethodsFour hundred and forty-seven histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 961 tumor-free controls were enrolled into the study. Five tag SNPs (rs6119954, rs1569686, rs4911107, rs4911259 and rs8118663) of the DNMT3b gene were genotyped by TaqMan assay. DNMT3b expression was evaluated in 104 cancer tissues by immunohistochemistry method.ResultsThe median follow-up time for 422 gastric patients with prognosis information was 55.1 (51.8–58.5) month. We found that individuals with the rs1569686 variant genotype (TG/GG) were significantly associated with poor prognosis in gastric cancer compared to those carrying the TT genotype (HR = 1.43, 95%CI: 1.02–1.99). This trend was more evident in the long-term survival of gastric cancer. Similar results were observed for the G allele carriers of rs4911107 and T allele carriers of rs4911259 as these two sites were in complete linkage disequilibrium with rs1569686. The rs8118663 GG carriers tended to live shorter than AA/AG genotype (HR = 2.72, 95%CI: 1.45–5.12) in patients living longer than 2.0 years. None of the five SNPs was associated with the risks of gastric cancer or gastric atrophy. And no relationship was found between each of the five SNPs and DNMT3b expression.ConclusionsThis study provides evidence that DNMT3b polymorphisms may predict long-term survival of gastric cancer. However, further studies are needed to reveal the underlying biological roles of DNMT3b polymorphism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Lee et al [ 35 ] found C alleles of DNMT3B contributed to the susceptibility of lung cancer in Korean population. Some other SNPs of DNMT3B, such as −579 G/T and −283 T/C, were also researched by some studies on their association with cancer risk [ 11 , 12 , 14 , 19 , 36 , 37 ]. However, there were only a very limited number of studies available for some SNPs and therefore not having enough statistical power to explore the real association.…”

Section: Discussionmentioning

confidence: 99%

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

Zhu

Zhang

et al. 2014

Med Oncol

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Published data on the association between DNA methyltransferase (DNMT) 3B −149C/T polymorphism and cancer risk remain inconclusive. To derive a more precise estimation for this association, we performed a meta-analysis of 5,903 cancer cases and 8,132 controls from 22 published case–control studies. We used odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the strength of the association. Our meta-analysis suggested that DNMT3B −149C/T polymorphism was associated with the risk of head and neck cancer under heterozygote comparison (OR 0.73, 95 % CI 0.59–0.90) and dominant model (OR 1.75, 95 % CI 0.62–0.92), although no evidence of association between DNMT3B −149C/T polymorphism and cancer risk was observed as we compared in the pooled analyses (homozygote comparison: OR 0.96, 95 % CI 0.86–1.09; heterozygote comparison: OR 1.07, 95 % CI 0.86–0.32; dominant model: OR 1.03, 95 % CI 0.85–1.25; recessive model: OR 0.93, 95 % CI 0.8–1.08). More studies are needed to detect DNMT3B −149C/T polymorphism and its association with cancer in different ethnic populations incorporated with environment exposures in the susceptibility of different kinds of cancer.

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“…Interestingly, the frequency of the DNMT3B -579G allele in Asians is much lower than that of the DNMT3B -579T one [ 22 ]. However, to the best of our knowledge, previous studies have assessed the role of this polymorphism in many different cancers, including those of the gastro-intestinal and respiratory apparatuses, head and neck carcinomas, and nasopharyngeal carcinomas [ 14 - 21 ], but never in thymoma, either alone or associated to MG.…”

Section: Discussionmentioning

confidence: 99%

“…The goal of the present study was to investigate if a common polymorphism ( -579G>T : rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, one of the key de novo enzymes mediating DNA methylation, increases the risk to develop MG or MG-associated thymomas. The selected polymorphism has been suggested to impair DNA methylation of tumor suppressor genes, therefore impairing their expression levels, and for this reason it was investigated as a susceptibility factor for several cancer types [ 16 - 21 ]. A meta-analysis of published studies revealed that the mutant allele (T) is associated with increased risk of cancer compared to the wild type one (G) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis

et al. 2013

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Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (thymomas) are present in about 10-20% of the patients, and there is indication that changes in DNA methylation might contribute to the risk and progression of thymomas. However, the role of epigenetics in MG is still not completely clarified. In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas. The study polymorphism was selected based on recent reports and a literature meta-analysis suggesting association with increased risk of various types of cancer. We screened 324 AChR+ MG patients (140 males and 184 females, mean age 56.0 ± 16.5 years) and 735 healthy matched controls (294 males and 441 females, mean age 57.3 ± 15.6 years). 94 of the total MG patients had a thymoma. While there was no association with the whole cohort of MG patients, we found a statistically significant association of the DNMT3B -579T allele (OR = 1.51; 95% CI=1.1-2.1, P = 0.01) and the TT homozygous genotype (OR = 2.59; 95% CI=1.4-4.9, P = 0.006) with the risk of thymoma. No association was observed in MG patients without thymoma, even after stratification into clinical subtypes. Present results suggest that the DNMT3B -579T allele might contribute to the risk of developing thymoma in MG patients, particularly in homozygous TT subjects.

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Gene expression and promoter polymorphisms of DNA methyltransferase 3B in nasopharyngeal carcinomas in Taiwanese people: A case-control study

Cited by 9 publications

References 26 publications

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

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

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

Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis

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