Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

Xiong, Hua; Liu, Xun-Qi; Sun, Ai-Hua; He, Ying; Li, Jun; Yuan, Xianglin

doi:10.7314/apjcp.2013.14.5.3139

Cited by 22 publications

(13 citation statements)

References 15 publications

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“…In addition, novel studies have demonstrated that MTHFR C677T polymorphisms could influence the methylation of MGMT, a gene which was associated with TNM stages of gastric cancer and used as a predictive biomarkers for detecting of gastric cancer. Taken together, these results may further demonstrated the previous results and provided a new insight in prevention of gastric cancer (Chen et al, 2012;Gao et al, 2013;Xiong et al, 2013).…”

Section: Discussionsupporting

confidence: 71%

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Fang

Xu²,

Huang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism

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Section: Discussionsupporting

confidence: 71%

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Fang

Xu²,

Huang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The MTHFR is an important enzyme in the one-carbon metabolism pathway that regulates the availability of methyl groups for methylation reactions, and several experimental and epidemiologic studies showed that the MTHFR C677T polymorphism may influence the DNA methylation status [21,23,52]. It has been shown that patients with the MTHFR TT677 genotype have a high risk of DNA hypermethylation in cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer

Ferlazzo

Currò

Zinellu

et al. 2017

IJMS

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Genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) enzyme may influence DNA methylation. Alterations in DNA methylation patterns of genes involved in the regulation of the cell cycle, DNA repair, cell adherence and metastasis process are known to contribute to cancer development. In this study, the influence of the MTHFR C677T and A1298C gene polymorphisms on global DNA methylation and site-specific methylation on p16 and O6-methylguanine-DNA methyltransferase (MGMT) gene promoters was investigated in patients with oral squamous cell cancer (OSCC). To this aim, methylation studies were carried out by using genomic DNA isolated from saliva samples of 58 OSCC patients and 90 healthy controls. The frequency of the CT/AC and TT/AA genotypes was significantly higher in patients than in controls. Whereas no difference in global DNA methylation levels was observed between patients and controls, a higher frequency of methylation at both p16 and MGMT gene promoters was detected in patients compared with controls. A significant association between MTHFR gene polymorphisms and p16 and MGMT gene promoter methylation was found. The frequency of p16 and MGMT methylation was around 60% in patients with either the CT/AC or TT/AA genotype. Our results suggest that hypermethylation of cancer-related genes may be affected by MTHFR polymorphisms.

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“…Numerous genes have been found to be methylated in GC, including hMLH1, p16, RUNX3, DAPK1, SFRP2 and RNF180. hMLH1 encodes DNA repair proteins and is closely associated with poor prognosis of GC patients; the frequency and specificity were found to be 8.6–80 and 4.1–80%, respectively (17–19). P16 inhibits cell cycle progression, and has been found to correlate with poor tumor differentiation, lymph node metastasis and poor survival.…”

Section: Discussionmentioning

confidence: 99%

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Xie

Sun

et al. 2014

Oncology Letters

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Gastric cancer (GC) is one of the most frequently diagnosed malignancies in East Asia, particularly in China, and remains the second leading cause of cancer-associated mortality worldwide. However, no effective plasma biomarkers have been identified for the diagnosis of patients with GC. The aim of this study was to investigate the DNA methylation status of the ring finger protein 180 (RNF180), secreted frizzled-related protein 2 (SFRP2) and death-associated protein kinase 1 (DAPK1) genes in the plasma samples of 57 GC patients and 42 control individuals with no malignant disease, and to evaluate the clinical utility of these makers. A significantly higher level of methylation was observed in the plasma DNA of GC patients when compared with that of controls for the three genes investigated (RNF180, 57.89% vs. 23.81%; DAPK1, 49.12% vs. 28.57%; and SFRP2, 71.93% vs. 42.86%). No association was identified between the DAPK1 or SFRP2 methylation level in the plasma DNA and the clinicopathological parameters of patients. Notably, RNF180 methylation was found to positively correlate with tumor size (P=0.018), histological type (P=0.025), TNM stage (P=0.002), lymph node metastasis (P=0.008) and distant metastasis (P=0.018). Overall, 50 cancer patients (87.72%) exhibited methylation of at least one of the three markers, while 26 normal subjects presented methylation in plasma DNA [specificity, 38.1%; odds ratio (OR), 4.4]. The combined use of RNF180 and SFRP2 as methylation markers appeared to be the most preferable predictor with regard to predictive power and cost-performance (OR, 5.57; P=0.0002). The results of the present study indicate that aberrant promoter methylation of genes in the plasma may be detected in a substantial proportion of GC patients and thus, these genes must be evaluated in the screening and surveillance of GC.

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Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

Cited by 22 publications

References 15 publications

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

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