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

Ericson, Ulrika LU ; Ivarsson, Malin Il; Sonestedt, Emily LU ; Gullberg, Bo LU ; Carlson, Joyce LU ; Olsson, Håkan LU and Wirfält, Elisabet LU (2009) In The American journal of clinical nutrition 90. p.1380-1389
Abstract
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The American journal of clinical nutrition
volume
90
pages
1380 - 1389
publisher
American Society for Clinical Nutrition
external identifiers
  • wos:000270959500035
  • pmid:19759169
  • scopus:70350639213
ISSN
1938-3207
DOI
10.3945/ajcn.2009.28064
language
English
LU publication?
yes
id
e0c3b8af-dae5-4aef-a23e-a8e124f8af48 (old id 1483392)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19759169?dopt=Abstract
date added to LUP
2009-10-07 11:37:45
date last changed
2017-02-12 04:20:58
@article{e0c3b8af-dae5-4aef-a23e-a8e124f8af48,
  abstract     = {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&lt;--T (rs1801133) and 1298A&lt;--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&lt;--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.},
  author       = {Ericson, Ulrika and Ivarsson, Malin Il and Sonestedt, Emily and Gullberg, Bo and Carlson, Joyce and Olsson, Håkan and Wirfält, Elisabet},
  issn         = {1938-3207},
  language     = {eng},
  pages        = {1380--1389},
  publisher    = {American Society for Clinical Nutrition},
  series       = {The American journal of clinical nutrition},
  title        = {Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele.},
  url          = {http://dx.doi.org/10.3945/ajcn.2009.28064},
  volume       = {90},
  year         = {2009},
}