C677T and A1298C methylenetetrahydrofolate reductase polymorphisms and breast cancer susceptibility among Latinos: a meta-analysis

Breast Cancer. 2019 Sep;26(5):602-611. doi: 10.1007/s12282-019-00961-8. Epub 2019 Mar 15.

Abstract

Background: Previous meta-analyses have shown an ethnic dependency of the C677T and the A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms, with no focus on the Latino population. For Latinos, many studies have examined these polymorphisms and breast cancer susceptibility, yielding no concise result. Therefore, we undertook this meta-analysis to determine the effect these polymorphisms have on breast cancer risk for Latinos.

Methods: PubMed, EBSCO, LILACS, Scopus, and Latin American-specific databases were searched for studies exploring the association between the MTHFR polymorphisms and breast cancer susceptibility in Latinos until January 2019. Genotype distributions were extracted and, depending on the level heterogeneity determined by the ψ2-based Q test and the I2 test, fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar's test and Egger's test.

Results: Of the 280 retrieved publications, 9 studies were included: 9 for the C677T polymorphism and 5 for the A1298C polymorphism. For the C677T polymorphism, there was an elevated risk for the homozygous (OR 1.42, 95% CI 1.05-1.92), the dominant (OR 1.16, 95% CI 1.02-1.31), the recessive (OR 1.33, 95% CI 1.01-1.75), and the allelic model (OR 1.17, 95% CI 1.03-1.33, p < 0.01). No association between the A1298C polymorphism and the risk to develop breast cancer was determined.

Conclusion: The results indicated that, for Latinos, the C677T polymorphism is associated with a significant risk for developing breast cancer, whereas the A1289C polymorphism does not.

Keywords: Carcinogenesis; Latin America; MTHFR; Mutation.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / ethnology*
  • Carcinogenesis / genetics
  • Exons / genetics
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Genotype
  • Hispanic or Latino / genetics*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Publication Bias
  • Risk

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)