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

Jolanta Lissowska, Mia M. Gaudet, Louise A. Brinton, Stephen J. Chanock, Beata Peplonska, Robert Welch, Witold Zatonski, Neonila Szeszenia-Dabrowska, Sue Park, Mark Sherman, Montserrat Garcia-Closas

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94 Scopus citations

Abstract

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 ah 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.

Original languageEnglish (US)
Pages (from-to)2696-2703
Number of pages8
JournalInternational Journal of Cancer
Volume120
Issue number12
DOIs
StatePublished - Jun 15 2007

Keywords

  • Breast cancer
  • Folate metabolism
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lissowska, J., Gaudet, M. M., Brinton, L. A., Chanock, S. J., Peplonska, B., Welch, R., Zatonski, W., Szeszenia-Dabrowska, N., Park, S., Sherman, M., & Garcia-Closas, M. (2007). Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: A population-based case-control study and meta-analyses. International Journal of Cancer, 120(12), 2696-2703. https://doi.org/10.1002/ijc.22604