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Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses.

Authors: Lissowska, J  Gaudet, MM  Brinton, LA  Chanock, SJ  Peplonska, B  Welch, R  Zatonski, W  Szeszenia-Dabrowska, N  Park, S  Sherman, M  Garcia-Closas, M 
Citation: Lissowska J, etal., Int J Cancer. 2007 Jun 15;120(12):2696-703.
Pubmed: (View Article at PubMed) PMID:17311260
DOI: Full-text: DOI:10.1002/ijc.22604

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.


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RGD Object Information
RGD ID: 2300328
Created: 2008-09-12
Species: All species
Last Modified: 2008-09-12
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.