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Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk.

Abstract

BACKGROUND

Evidence from case-control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a meta-analysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk.

METHODS

We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case-control studies or relative risks (RRs) for cohort studies for a 100-microg/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies.

RESULTS

A total of 13 case-control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confidence interval [CI] = 0.87 to 0.96) from the case-control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100-microg/d increase in folate intake. We found evidence that the case-control studies may have suffered from substantial publication bias. The case-control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case-control studies were potentially subject to recall bias and publication bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk.

CONCLUSION

A lack of dietary folate intake is not associated with the risk of breast cancer.

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  • Authors+Show Affiliations

    ,

    Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. s.j.lewis@bristol.ac.uk

    , ,

    Source

    Journal of the National Cancer Institute 98:22 2006 Nov 15 pg 1607-22

    MeSH

    5,10-Methylenetetrahydrofolate Reductase (FADH2)
    Breast Neoplasms
    Case-Control Studies
    Cytosine
    Dietary Supplements
    Female
    Folic Acid
    Homozygote
    Humans
    Odds Ratio
    Polymorphism, Genetic
    Risk Assessment
    Risk Factors
    Thymine

    Pub Type(s)

    Journal Article
    Meta-Analysis

    Language

    eng

    PubMed ID

    17105984

    Citation

    Lewis, Sarah J., et al. "Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk." Journal of the National Cancer Institute, vol. 98, no. 22, 2006, pp. 1607-22.
    Lewis SJ, Harbord RM, Harris R, et al. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst. 2006;98(22):1607-22.
    Lewis, S. J., Harbord, R. M., Harris, R., & Smith, G. D. (2006). Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. Journal of the National Cancer Institute, 98(22), pp. 1607-22.
    Lewis SJ, et al. Meta-analyses of Observational and Genetic Association Studies of Folate Intakes or Levels and Breast Cancer Risk. J Natl Cancer Inst. 2006 Nov 15;98(22):1607-22. PubMed PMID: 17105984.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. AU - Lewis,Sarah J, AU - Harbord,Roger M, AU - Harris,Ross, AU - Smith,George Davey, PY - 2006/11/16/pubmed PY - 2006/12/9/medline PY - 2006/11/16/entrez SP - 1607 EP - 22 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 98 IS - 22 N2 - BACKGROUND: Evidence from case-control studies suggests that increasing dietary folate intake is associated with a reduced risk of breast cancer. However, large cohort studies have found no such association, and animal studies suggest that folate supplementation may promote tumorigenesis. We conducted a meta-analysis to summarize the available evidence from observational studies on this issue and a meta-analysis of the association between a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate metabolism, and breast cancer risk. METHODS: We searched Medline and ISI Web of Knowledge databases for relevant studies that were published through May 31, 2006. We used random-effects analysis to calculate odds ratios (ORs) for case-control studies or relative risks (RRs) for cohort studies for a 100-microg/d increase in folate intake. Unadjusted odds ratios were calculated for the studies of MTHFR genotype based on published genotype frequencies. RESULTS: A total of 13 case-control studies and nine cohort studies were included in the meta-analysis of folate intake and breast cancer risk. We found a summary OR of 0.91 (95% confidence interval [CI] = 0.87 to 0.96) from the case-control studies and a summary RR of 0.99 (95% CI = 0.98 to 1.01) from the cohort studies for a 100-microg/d increase in folate intake. We found evidence that the case-control studies may have suffered from substantial publication bias. The case-control and cohort studies may have been subject to measurement error, confounding, and possibly spurious associations arising from subgroup analyses; in addition, the case-control studies were potentially subject to recall bias and publication bias. Seventeen studies were included in the meta-analysis of MTHFR C677T genotype and breast cancer risk. We found no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes (OR = 1.05, 95% CI = 0.88 to 1.25), and there was no evidence of an interaction between folate intake and MTHFR genotype on breast cancer risk. CONCLUSION: A lack of dietary folate intake is not associated with the risk of breast cancer. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/17105984/Meta_analyses_of_observational_and_genetic_association_studies_of_folate_intakes_or_levels_and_breast_cancer_risk_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djj440 DB - PRIME DP - Unbound Medicine ER -