Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: A nested-case-control study and a pooled meta-analysis

Debora Macis, Patrick Maisonneuve, Harriet Johansson, Bernardo Bonanni, Edoardo Botteri, Simona Iodice, Barbara Santillo, Silvana Penco, Giacomo Gucciardo, Giuseppe D'Aiuto, Marco Rosselli Del Turco, Marinella Amadori, Alberto Costa, Andrea Decensi

Research output: Contribution to journalArticlepeer-review


Background: A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk. Methods: We conducted a nested case-control study within a phase III prevention trial of tamoxifen. After a median follow-up of 81.2 months, 79 of the 5,408 hysterectomised women aged 35-70 years, who had received either tamoxifen 20 mg/day or placebo for 5 years, developed breast cancer. A total of 46 breast cancer cases and 80 unaffected controls matched to treatment allocation, years from randomization (±2 years) and age at randomization (±5 years), underwent genotyping for MTHFR C677T polymorphism using real time PCR. Results: The MTHFR 677 genotype frequencies for CC, CT, TT in breast cancer cases were 30%, 44% and 26%, respectively, and 35%, 51%, 14% in controls. We observed a borderline significant odds ratio of 2.51 (95% CI, 0.96-6.55) of breast cancer in subjects with 677TT genotype, with no further association after stratifying for age and treatment group. A meta-analysis of 18 studies, including our own, showed an increased risk of breast cancer in premenopausal women with 677TT genotype, with an odds ratio of 1.42 (95% CI, 1.02-1.98). Conclusions: Our study lends support to a positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk. Additional studies are warranted to provide further insight into the role of folate metabolism deficiency and breast cancer.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - Dec 2007


  • Meta-analysis
  • Methylenetetrahydrofolate reductase
  • Nested case-control study

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: A nested-case-control study and a pooled meta-analysis'. Together they form a unique fingerprint.

Cite this