Methylenetetrahydrofolate Reductase A1298C Polymorphism and Breast Cancer Risk: A Meta-analysis of 33 Studies

Abstract

Methylenetetrahydrofolate reductase (MTHFR) enzyme is essential for DNA synthesis and DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and different types of cancers. Several studies have investigated the association between the MTHFR A1298C polymorphism and breast cancer (BC) risk, but the results were inconclusive. To assess the risk associated with MTHFR A1298C polymorphism, a comprehensive meta-analysis was performed. PubMed, Google Scholar, Elsevier and Springer Link databases were searched for case-control studies relating the association between MTHFR A1298C polymorphism and BC risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Up to January 2014, 33 case-control studies involving 15,919 BC patients and 19,700 controls were included in the present meta-analysis. The results showed that the A1298C polymorphism was not associated with BC risk in all the five genetic models (C vs. A allele (allele contrast): OR = 0.99, 95% confidence interval (CI): 0.93-1.05; AC versus AA (heterozygote/codominant): OR = 0.97, 95% CI: 0.89-1.04; CC versus AA (homozygote): OR = 0.99, 95% CI: 0.91-1.06; CC + AC versus AA (dominant model): OR = 0.97, 95% CI: 0.90-1.05; and CC versus AC + AA (recessive model): OR = 0.99, 95% CI: 0.91-1.07). The present meta-analysis did not support any association between the MTHFR A1298C polymorphism and BC risk.

Keywords: A1298C; Breast cancer; Folate; Meta-analysis; Methylenetetrahydrofolate reductase; Polymorphism.

Figure 1

Forest plot for the association between MTHFR A1298C polymorphism and Breast Cancer for allele contrast model (C vs A) with random effect model. Results of individual and summary OR estimates, 95% CI, and weights of each study were shown

Figure 2

Forest plot for the association between MTHFR A1298C polymorphism and Breast cancer for homozygote model (CC vs AA) with fixed effect model. Results of individual and summary OR estimates, 95% CI, and weights of each study were shown

Figure 3

Funnel plots, A. precision versus OR for allele contrast model, B. standard error versus OR for allele contrast model (C vs A). C precision versus OR for homozygote model, D. Standard error versus OR for homozygote model