MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls

Breast Cancer Res Treat. 2010 Sep;123(2):549-55. doi: 10.1007/s10549-010-0783-5. Epub 2010 Feb 9.

Abstract

Published data on the association between MTHFR C677T polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01-1.23; dominant model: OR = 1.04, 95% CI = 1.00-1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04-1.35; recessive model: OR = 1.15, 95% CI = 1.03-1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02-1.38; recessive model: OR = 1.17, 95% CI = 1.05-1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02-1.23; dominant model: OR = 1.11, 95% CI = 1.01-1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.

Publication types

  • Meta-Analysis

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Racial Groups / genetics
  • Risk Assessment
  • Risk Factors

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)