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Int. J. Mol. Sci. 2016, 17(12), 1996; doi:10.3390/ijms17121996

Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer

1
Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan
2
School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan
3
Department of Pharmacy, China Medical University, Taichung 404, Taiwan
4
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
5
Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
7
Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8
Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan
9
Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan
10
Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
11
Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
12
Department of Pharmacy, Tajen University, Pingtung 907, Taiwan
13
Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan
14
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
15
Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan
16
Department of Nursing, Asia University, Taichung 413, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 19 October 2016 / Revised: 18 November 2016 / Accepted: 24 November 2016 / Published: 29 November 2016
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
View Full-Text   |   Download PDF [1172 KB, uploaded 29 November 2016]   |  

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. View Full-Text
Keywords: prostate cancer; radical prostatectomy; recurrence; genetic variation; methylenetetrahydrofolate reductase prostate cancer; radical prostatectomy; recurrence; genetic variation; methylenetetrahydrofolate reductase
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Lin, V.C.; Lu, T.-L.; Yin, H.-L.; Yang, S.-F.; Lee, Y.-C.; Liu, C.-C.; Huang, C.-Y.; Yu, C.-C.; Chang, T.-Y.; Huang, S.-P.; Bao, B.-Y. Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer. Int. J. Mol. Sci. 2016, 17, 1996.

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