Tags

Type your tag names separated by a space and hit enter

Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele.
Am J Clin Nutr. 2009 Nov; 90(5):1380-9.AJ

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. 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.

Authors+Show Affiliations

Department of Clinical Sciences, Malmö, Nutrition Epidemiology, Lund University, Sweden. ulrika.ericson@med.lu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19759169

Citation

Ericson, Ulrika C., et al. "Increased Breast Cancer Risk at High Plasma Folate Concentrations Among Women With the MTHFR 677T Allele." The American Journal of Clinical Nutrition, vol. 90, no. 5, 2009, pp. 1380-9.
Ericson UC, Ivarsson MI, Sonestedt E, et al. Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. Am J Clin Nutr. 2009;90(5):1380-9.
Ericson, U. C., Ivarsson, M. I., Sonestedt, E., Gullberg, B., Carlson, J., Olsson, H., & Wirfält, E. (2009). Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. The American Journal of Clinical Nutrition, 90(5), 1380-9. https://doi.org/10.3945/ajcn.2009.28064
Ericson UC, et al. Increased Breast Cancer Risk at High Plasma Folate Concentrations Among Women With the MTHFR 677T Allele. Am J Clin Nutr. 2009;90(5):1380-9. PubMed PMID: 19759169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele. AU - Ericson,Ulrika C, AU - Ivarsson,Malin I L, AU - Sonestedt,Emily, AU - Gullberg,Bo, AU - Carlson,Joyce, AU - Olsson,Håkan, AU - Wirfält,Elisabet, Y1 - 2009/09/16/ PY - 2009/9/18/entrez PY - 2009/9/18/pubmed PY - 2010/1/7/medline SP - 1380 EP - 9 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 90 IS - 5 N2 - 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/19759169/Increased_breast_cancer_risk_at_high_plasma_folate_concentrations_among_women_with_the_MTHFR_677T_allele_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.2009.28064 DB - PRIME DP - Unbound Medicine ER -