Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 18; no. 9; pp. 2528 - 2539
• Main Authors: COLLIN, Simon M, METCALFE, Chris, NEAL, David E, HAMDY, Freddie C, GUDMUNDSSON, Julius, SULEM, Patrick, RAFNAR, Thorunn, BENEDIKTSDOTTIR, Kristrun R, EELES, Rosalind A, GUY, Michelle, KOTE-JARAI, Zsofia, MORRISON, Jonathan, ZUCCOLO, Luisa, OLAMA, Ali Amin Al, STEFANSSON, Kari, EASTON, Douglas F, MARTIN, Richard M, LEWIS, Sarah J, LINA CHEN, COX, Angela, DAVIS, Michael, LANE, J. Athene, DONOVAN, Jenny, DAVEY SMITH, George
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2009
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - metabolism; Biological and medical sciences; Case-Control Studies; folate-pathway; Folic Acid - metabolism; Genetic Predisposition to Disease; Glutamate Carboxypeptidase II - genetics; Glutamate Carboxypeptidase II - metabolism; Glycine Hydroxymethyltransferase - genetics; Glycine Hydroxymethyltransferase - metabolism; Humans; Male; Medical sciences; meta-analysis; Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics; Methylenetetrahydrofolate Dehydrogenase (NADP) - metabolism; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Minor Histocompatibility Antigens; Nephrology. Urinary tract diseases; one-carbon metabolism; Polymorphism, Genetic; prostate cancer; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Risk Factors; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Genetic variability; Prostate disease; Vitamin; Systematic review; Risk; Case control study; Epidemiology; Evidence-based medicine; Folic acid; Folate; Metaanalysis; Association; Cancerology; Male genital diseases; Public health; Urinary system disease; Statistical analysis; Evidence-based practice; Genotype; Malignant tumor; Statistical study; Risk factor; Prostate cancer; Bibliographic review; Cancer
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-09-0223

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 A 66G (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 FOLH 1 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.(Cancer Epidemiol Biomarkers Prev 2009;18(9):2528–39)