Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.
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.
Collin
Simon M
SM
Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS United Kingdom. simon.collin@bristol.ac.uk
Metcalfe
Chris
C
Zuccolo
Luisa
L
Lewis
Sarah J
SJ
Chen
Lina
L
Cox
Angela
A
Davis
Michael
M
Lane
J Athene
JA
Donovan
Jenny
J
Smith
George Davey
GD
Neal
David E
DE
Hamdy
Freddie C
FC
Gudmundsson
Julius
J
Sulem
Patrick
P
Rafnar
Thorunn
T
Benediktsdottir
Kristrun R
KR
Eeles
Rosalind A
RA
Guy
Michelle
M
Kote-Jarai
Zsofia
Z
Morrison
Jonathan
J
Al Olama
Ali Amin
AA
Stefansson
Kari
K
Easton
Douglas F
DF
Martin
Richard M
RM
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
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