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Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele.

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Author

Summary, in English

BACKGROUND: Folate is involved in DNA synthesis and methylation and may thereby influence carcinogenesis. OBJECTIVES: We examined plasma folate (P-folate) concentration in relation to genotypes of the folate-metabolizing enzyme methylenetetrahydrofolate reductase [MTHFR 677C<--T (rs1801133) and 1298A<--C (rs1801131)]. We also explored whether P-folate was associated with risk of postmenopausal breast cancer overall and in subgroups with genetic variants of the MTHFR single nucleotide polymorphisms (SNPs). DESIGN: This nested case-control study included 313 cases (age 55-73 y at baseline) with invasive breast cancer and 626 control subjects, matched on age and blood-sample date, from the population-based Malmö Diet and Cancer cohort. P-folate and MTHFR genotypes were determined for 310 cases and 611 controls. P-folate according to genotype was calculated by using analysis of variance. Odds ratios were obtained by using logistic regression. All tests were 2-sided. RESULTS: The variant 677T allele was associated with lower P-folate. In women with the 677T allele, a high P-folate concentration was associated with increased breast cancer risk (P for trend across P-folate tertiles = 0.03). Interaction was seen between the 677C<--T SNP and P-folate (P = 0.002). A positive association, which was seen between P-folate and breast cancer risk in 1298AA women (P = 0.01), was probably due to linkage between the 2 SNPs. Overall, and in women with other genotypes, no significant associations were observed. CONCLUSIONS: Our results suggest an association of high P-folate concentration with increased risk of postmenopausal breast cancer in carriers of the 677T allele. The findings underline the importance of genetic variation of MTHFR in the complex relation between folate and cancer.

Publishing year

2009

Language

English

Pages

1380-1389

Publication/Series

The American journal of clinical nutrition

Volume

90

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Nutrition and Dietetics

Status

Published

Research group

  • Nutrition Epidemiology
  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1938-3207