Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses.
Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk.
Lissowska
Jolanta
J
Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland. lissowsj@coi.waw.p
Gaudet
Mia M
MM
Brinton
Louise A
LA
Chanock
Stephen J
SJ
Peplonska
Beata
B
Welch
Robert
R
Zatonski
Witold
W
Szeszenia-Dabrowska
Neonila
N
Park
Sue
S
Sherman
Mark
M
Garcia-Closas
Montserrat
M
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015201:Meta-Analysis as Topic; D053858:Metabolic Networks and Pathways; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein
D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D002244:Carbon; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; D003541:Cystathionine beta-Synthase