|Title:||Prognostic relevance of methylenetetrahydrofolate reductase polymorphisms for prostate cancer||Authors:||Lin V.C.
|Keywords:||Genetic variation; Methylenetetrahydrofolate reductase; Prostate cancer; Radical prostatectomy; Recurrence||Issue Date:||2016||Publisher:||MDPI AG||Journal Volume:||17||Journal Issue:||12||Start page/Pages:||1996||Source:||International Journal of Molecular Sciences||Abstract:||
Folate metabolism has been associated with cancers via alterations in nucleotide synthesis, DNA methylation, and DNA repair. We hypothesized that genetic variants in methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate metabolism, would affect the prognosis of prostate cancer. Three haplotype-tagging single-nucleotide polymorphisms (SNPs) across the MTHFR gene region were genotyped in a cohort of 458 patients with clinically localized prostate cancer treated with radical prostatectomy. One SNP, rs9651118, was associated with disease recurrence, and the association persisted after multivariate analyses adjusting for known risk factors. Public dataset analyses suggested that rs9651118 affects MTHFR expression. Quantitative real-time polymerase chain reaction analysis revealed that MTHFR expression is significantly upregulated in prostate tumor tissues when compared with adjacent normal tissues. Furthermore, overexpression of MTHFR correlates with cancer recurrence and death in two independent publicly available prostate cancer datasets. In conclusion, our data provide rationale to further validate the clinical utility of MTHFR rs9651118 as a biomarker for prognosis in prostate cancer. ? 2016 by the authors; licensee MDPI, Basel, Switzerland.
|ISSN:||1661-6596||DOI:||10.3390/ijms17121996||SDG/Keyword:||5,10 methylenetetrahydrofolate reductase (FADH2); genomic DNA; prostate specific antigen; methylenetetrahydrofolate reductase (NADPH2); 5,10 methylenetetrahydrofolate reductase (FADH2) gene; adult; Article; cancer prognosis; cancer specific survival; cancer staging; cohort analysis; controlled study; DNA isolation; DNA microarray; female; gene; gene overexpression; genotype; Gleason score; human; human tissue; lymph node metastasis; major clinical study; male; prostate cancer; prostatectomy; real time polymerase chain reaction; recurrent disease; single nucleotide polymorphism; upregulation; genetic polymorphism; genetic predisposition; genetics; haplotype; pathology; prognosis; Prostatic Neoplasms; single nucleotide polymorphism; tumor recurrence; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Neoplasm Recurrence, Local; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Prostatectomy; Prostatic Neoplasms
|Appears in Collections:||醫學系|
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