The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: A systematic review and meta-analysis

Ge, Wenzhang; Jiao, Yang; Chang, Lianzhen

doi:10.1371/journal.pone.0202959

Cited by 10 publications

(5 citation statements)

References 42 publications

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“…It was found that MTHFD is irreversibly converted to 5-MeTHF in the intracellular folate metabolism and methionine-homocysteine cycle by the critical enzyme MTHFR [25]. A meta-analysis revealed a statistically significant connection between MTHFR gene polymorphisms and the risk of developing OSCC [26]. is indicates that MTHFD family genes promote cancer progression through interacting with other metabolizing enzymes.…”

Section: Discussionmentioning

confidence: 99%

The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma

Wang

Tang

et al. 2022

Journal of Oncology

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Objective. To investigate the function and regulatory mechanisms of methylenetetrahydrofolate dehydrogenase (MTHFD) family genes in oral squamous cell carcinoma (OSCC), especially focus on their regulating role in tumor immunity. Methods. The publicly available data from the TCGA database were used to investigate the expression pattern and regulatory role of MTHFD family genes in OSCC. More importantly, the involvement of MTHFD family genes in tumor immunity was investigated in terms of immune and stromal cell infiltration in tumor microenvironment, tumor-infiltrating immune cells, and immunomodulatory genes (e.g., immunoinhibitory genes and immunostimulatory genes). Statistical analysis was performed using R software packages and public web servers. Results. MTHFD family genes were considerably upregulated in OSCC as compared with normal oral tissue. Patients with high MTHFD2 expression presented worse survival outcomes than those with low MTHFD2 expression. Functional enrichment analysis showed that the top 100 positively and negatively correlated genes of the MTHFD family genes were significantly enriched in several KEGG pathways, including cell cycle, spliceosome, DNA replication, and Th17 cell differentiation. As a result of tumor immunity analysis, MTHFD2L expression was found to be negatively related to the Estimate-Stromal-Immune score in OSCC; however, there was no statistical significance between the Estimate-Stromal-Immune score and MTHFD1, MTHFD1L, or MTHFD2 in OSCC. Additionally, MTHFD family genes were found to be significantly positively correlated with tumor-infiltrating immune cells, including Treg and Th17 cells. Moreover, MTHFD family genes were significantly correlated with several immune inhibitory genes such as CD274 and CTLA4 and several immune-stimulatory genes such as CXCL12, CXCR4, and TMIGD2. Conclusion. Given the expression pattern, prognostic value, biological functions, and involvement in tumor immunity, MTHFD family genes could serve as potential therapeutic biomarkers in targeting tumor immunity in oral cancer.

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Section: Discussionmentioning

confidence: 99%

The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma

Wang

Tang

et al. 2022

Journal of Oncology

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“…While we expected to observe a more profound difference between our DF and SF groups, it is conceivable that environmental factors, like diet, must interact with genetics to observe an effect. For example, polymorphisms in the gene for methylenetetrahydrofolate reductase, encoded by MTHFR, are clearly linked to increased risk of oral SCC, as illuminated by a meta‐analysis of 13 human studies involving data from 1539 oral SCC patients and 2131 controls (Ge et al, 2018). They found that the T allele, and in particular the TT genotype, of MTHFR C677T polymorphism was linked to increased risk of oral SCC.…”

Section: Discussionmentioning

confidence: 99%

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer

Pitstick,

Goral,

Ciancio

et al. 2023

Oral Diseases

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ObjectivesTo investigate the effects of dietary folate and sex on histopathology of oral squamous cell carcinoma in mice.Materials and MethodsMice (C57Bl/6, 30/sex) were fed either a deficient folate or sufficient folate diet. Vehicle or 4‐nitroquinoline1‐oxide (50 μg/mL) in vehicle were administered in drinking water for 20 weeks, followed by 6 weeks of regular drinking water. Oral lesions were observed weekly. Tongues were studied for histopathologic changes. Immunohistochemical techniques were used to measure cell proliferation (Ki67+), and to quantify expression of folate receptor, reduced folate carrier, and proton‐coupled folate transporter. T cells, macrophages, and neutrophils were counted and normalized to area.ResultsAll 4NQO‐treated mice developed oral tumors. Dietary folate level did not affect tumor burden. More tumors were observed on the ventral aspect of the tongue than in other locations within the oral cavity. 4‐nitroquinoline‐1‐oxide‐treated mice displayed 27%–46% significantly lower expression of all three folate transport proteins; diet and sex had no effect on folate transporter expression. T‐cell and neutrophil infiltration in tongues were 9.1‐fold and 18.1‐fold increased in the 4‐nitroquinoline‐1‐oxide‐treated mouse tongues than in controls.ConclusionTreatment with 4NQO was the primary factor in determining cancer development, decreased folate transport expression, and lymphoid cell infiltration.

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“…The T allele and the TT genotype have been associated with other oral disease contexts, including lichen planus and squamous cell carcinoma. 29,30 The enzyme encoded by this gene participates in the folate metabolism pathway, which produces the SAM radicals used by the DNMTs as methyl donors for DNA methylation. Marinho, et al 32 (2019).…”

Section: Methylation Profile Analysismentioning

confidence: 99%

miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis

et al. 2020

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miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and-149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism-149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

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The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: A systematic review and meta-analysis

Cited by 10 publications

References 42 publications

The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma

The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer

miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis

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