title: Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer.
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 theMTHFRgene 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 affectsMTHFRexpression. Quantitative real-time polymerase chain reaction analysis revealed thatMTHFRexpression is significantly upregulated in prostate tumor tissues when compared with adjacent normal tissues. Furthermore, overexpression ofMTHFRcorrelates 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 ofMTHFRrs9651118 as a biomarker for prognosis in prostate cancer.
authors.affiliation: Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan. victorlin0098@yahoo.com.tw.|School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan. victorlin0098@yahoo.com.tw.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, China Medical University, Taichung 404, Taiwan. lutl@mail.cmu.edu.tw.
authors.forename: Te-Ling
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. schoolyin@gmail.com.|Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. schoolyin@gmail.com.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yin
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. sfyang@kmu.edu.tw.|Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. sfyang@kmu.edu.tw.
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. leeyc12345@yahoo.com.tw.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. leeyc12345@yahoo.com.tw.
authors.forename: Yung-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. m8201055@yahoo.com.tw.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. m8201055@yahoo.com.tw.
authors.forename: Chia-Chu
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan. cyhuang0909@ntu.edu.tw.|Department of Urology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan. cyhuang0909@ntu.edu.tw.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. ccyu@vghks.gov.tw.|Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. ccyu@vghks.gov.tw.|Department of Pharmacy, Tajen University, Pingtung 907, Taiwan. ccyu@vghks.gov.tw.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Occupational Safety and Health, China Medical University, Taichung 404, Taiwan. tychang@mail.cmu.edu.tw.
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. shpihu@yahoo.com.tw.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung 404, Taiwan. bao@mail.cmu.edu.tw.|Sex Hormone Research Center, China Medical University Hospital, Taichung 404, Taiwan. bao@mail.cmu.edu.tw.|Department of Nursing, Asia University, Taichung 413, Taiwan. bao@mail.cmu.edu.tw.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: genetic variation; methylenetetrahydrofolate reductase; prostate cancer; radical prostatectomy; recurrence