MTHFR c.677C&gt;T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai

Wu, Jun; Zhou, Shu; Zhao, Rui; Zhang, Xuan; Chang, Kun; Gu, Cheng; Gan, Hua; Dai, Bo; Zhu, Yao; Zhang, Hai Liang; Shi, Guo Hai; Qu, Yuan; Zhao, Jian; Ye, Ding Wei

doi:10.1038/srep36290

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…Furthermore, the sample sizes were relatively small in most of included studies. A functional study indicated that MTHFR rs1801133 G>A polymorphism was a protective factor of prostate cancer (PC) susceptibility by elevating homocysteine level, promoting cell apoptosis, and inhibiting proliferation of PC cells [ 21 ]. In the present study, we found that MTHFR rs1801133 A allele might be a protective factor for NSCLC, which was similar to the findings of previous study conducted in Eastern Chinese Han populations.…”

Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population

Ding

Wang²,

Chen

et al. 2017

Oncotarget

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Previous reports implicated 5,10-ethylenetetrahydrofolate reductase (MTHFR) polymorphisms acted as a potential risk factor for several cancers. In order to explore the effect of MTHFR SNPs on non-small cell lung cancer (NSCLC), we selected MTHFR tagging single nucleotide polymorphisms (SNPs) and carried out a case-control study to determine the potential relationship of MTHFR SNPs with NSCLC risk. Our study consisted of 521 NSCLC patients and 1,030 non-cancer controls. MTHFR SNPs were genotyped by SNPscanTM genotyping assay. Using four genetic models (additive, Homozygote, dominant, recessive), the genotype frequencies were compared using the chi-squared (χ2) test. Crude/adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the difference for the genotype distribution. We found that MTHFR rs1801133 G>A polymorphism decreased the risk of overall NSCLC. In a subgroup analysis, MTHFR rs1801133 G>A polymorphism also decreased NSCLC risk in female, < 60 years and never smoking subgroups. However, we identified that MTHFR rs4845882 G>A polymorphism was associated with the development of NSCLC in female subgroup. In addition, MTHFR rs9651118 T>C polymorphism increased the risk of NSCLC in < 60 years, never smoking and BMI < 24 kg/m2 subgroups. In conclusion, the current study highlights MTHFR rs1801133 G>A variants decreases the risk of NSCLC. Nevertheless, MTHFR rs4845882 G>A and rs9651118 T > C polymorphisms may be associated with NSCLC susceptibility. Well-designed large-scale studies are needed to confirm these findings and explore the interactions of gene-gene and gene-environment involved in MTHFR SNPs and NSCLC.

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Section: Discussionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population

Ding

Wang²,

Chen

et al. 2017

Oncotarget

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“…In cells with DNA damage, negatively charged DNA fragments are released from the nucleus and migrate towards the anode. 16 The restoration of miR-375 resulted in a significant increase in DNA damage compared to that inducted by the scrambled control or miR-NC ( Figure 4C and Ds). Interestingly, we also observed that scratch closure and cell proliferation were significantly inhibited in MG63 cells transfected with miR-375-mimics ( Figure 4A, B and E).…”

Section: Mir-375 Modulates Cis-induced Dna Damage In Mg63 Cells and Amentioning

confidence: 87%

<p>A Chemotherapy-Driven Increase in Mcl-1 Mediates the Effect of miR-375 on Cisplatin Resistance in Osteosarcoma Cells</p>

Liu¹,

Yu²,

Yang³

et al. 2019

OTT

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Background: Osteosarcoma (OS) is one of the most difficult cancers to treat due to its resistance to chemotherapy. The essential role played by Mcl-1 in promoting chemoresistance has been observed in a variety of cancers, including OS, while the underlying mechanism remains unclear. Methods: We investigated the expression of Mcl-1 in 42 paired OS specimens obtained before and after adjuvant chemotherapy, and its correlation with clinicopathological characteristics. Loss and gain of function studies were performed to analyze the effects of Mcl-1 modulations on the chemosensitivity, and the mechanism involved in the deregulation of Mcl-1 in OS cells. Results: In OS specimens, the expression of Mcl-1 was significantly upregulated after chemotherapy, and high Mcl-1 expression was associated with poorer overall survival and an increased recurrence rate. Furthermore, we demonstrated that chemotherapy-driven increased Mcl-1 decreased chemosensitivity by promoting tumour proliferation and inhibiting DNA damage. Moreover, Mcl-1 was found to be a direct target of miR-375 in OS cells. The knockdown of Mcl-1 phenocopied miR-375 downregulation, and the overexpression of miR-375 rescued the effects of cisplatin-induced DNA damage mediated by Mcl-1. Conclusion: Our data indicated that chemotherapy-driven increase in the expression of Mcl-1 plays a critical role in chemoresistance, and the intervention of the miR-375/Mcl-1 axis may offer a novel strategy to enhance chemosensitivity in OS treatment.

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“…A number of studies were conducted to check the association of MTHFR C677T gene polymorphism with the prostate cancer [35-47]. Very few studies were published, which evaluated MTRR A66G polymorphism as risk for prostate cancer [39,40,48-50].…”

Section: Introductionmentioning

confidence: 99%

Folate (MTHFRC677T andMTRRA66G) gene polymorphisms and risk of prostate cancer: a case-control study with an updated meta-analysis

Yadav

Kumar

Dwivedi

et al. 2021

Preprint

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IntroductionMethylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the key enzymes of the folate pathway, which involved in the DNA methylation. DNA methylation may affect the stability and integrity of DNA, that supposed to play a pivotal role in carcinogenesis. So, we aimed to investigate the association of MTHFR C677T and MTRR A66G gene polymorphisms with susceptibility to prostate cancer in North Indian population. We also performed meta-analyses of published literatures on these polymorphisms to evaluate their association with prostate cancer.MethodsWe genotyped MTHFR C677T and MTRR A66G gene polymorphisms in 147 prostate cancer cases and 147 healthy controls using PCR-RFLP methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for risk estimation. For meta-analysis different databases were searched and all statistical analysis were performed using Open Meta-Analyst software.ResultsThe present case control study revealed that the T allele (OR= 1.67; 95% CI: 0.99-2.84, p= 0.05), CT genotype (OR= 1.92; 95% CI: 1.06-3.48, p= 0.02), and dominant (TT+CT) model (OR= 1.85; 95% CI: 1.05-3.30, p= 0.03) of MTHFR C677T gene polymorphism and G allele (OR= 1.92; 95% CI: 1.35-2.73, p= 0.0002) of MTRR A66G gene polymorphism were significantly associated with prostate cancer susceptibility. Meta-analyses of MTHFR C677T and MTRR A66G gene polymorphisms showed no significant association between these polymorphisms and prostate cancer risk in overall or in subgroup meta-analysis stratified by ethnicity.ConclusionMTHFR C677T and MTRR A66G gene polymorphisms seem to play a significant role in prostate cancer susceptibility in North Indian population, while results of meta-analysis revealed no association between MTHFR C677T and MTRR A66G gene polymorphisms and prostate cancer susceptibility.

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MTHFR c.677C>T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai

Cited by 9 publications

References 36 publications

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population

<p>A Chemotherapy-Driven Increase in Mcl-1 Mediates the Effect of miR-375 on Cisplatin Resistance in Osteosarcoma Cells</p>

Folate (MTHFRC677T andMTRRA66G) gene polymorphisms and risk of prostate cancer: a case-control study with an updated meta-analysis

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