title: Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.
abstract: Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a case-control study nested within the UK population-based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight polymorphisms: MTHFR C677T (rs1801133; 12 studies; 10,745 cases; 40,158 controls), MTHFR A1298C (rs1801131; 5 studies; 3,176 cases; 4,829 controls), MTR A2756G (rs1805087; 8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 controls), and FOLH1 T1561C (rs202676; 5 studies; 6,314 cases; 35,190 controls). The majority (10 of 13) of eligible studies had 100% Caucasian subjects; only one study had <90% Caucasian subjects. We found weak evidence of dominant effects of two alleles: MTR 2756A>G [random effects pooled odds ratio, 1.06 (1.00-1.12); P = 0.06 (P = 0.59 for heterogeneity across studies)] and SHMT1 1420C>T [random effects pooled odds ratio, 1.11 (1.00-1.22); P = 0.05 (P = 0.38 for heterogeneity across studies)]. We found no effect of MTHFR 677C>T or any of the other alleles in dominant, recessive or additive models, or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on advanced or localized cancers. Our meta-analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer.
authors.affiliation: Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS United Kingdom. simon.collin@bristol.ac.uk
authors.forename: Simon M
authors.initials: SM
authors.lastname: Collin
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
authors.forename: J Athene
authors.initials: JA
authors.lastname: Lane
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: Julius
authors.initials: J
authors.lastname: Gudmundsson
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Kristrun R
authors.initials: KR
authors.lastname: Benediktsdottir
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: Michelle
authors.initials: M
authors.lastname: Guy
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Jonathan
authors.initials: J
authors.lastname: Morrison
authors.forename: Ali Amin
authors.initials: AA
authors.lastname: Al Olama
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D015778:Minor Histocompatibility Antigens; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human; D043425:Glutamate Carboxypeptidase II