Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies

Abstract

Background: The associations between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial.

Methodology/principal findings: An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effect model (FEM) or random-effect model (REM), depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007). No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies.

Conclusion: A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk.

Figure 1. Flow diagram of the literature search.

Figure 2. Forest plots of association of Fok1 polymorphism with breast cancer.

Significant association was detected between the genotype ff and breast cancer in recessive model (ff vs. Ff+FF). The squares and horizontal lines correspond to OR and 95% CI of specific study, and the area of squares reflects study weight. The diamond represents the pooled OR and 95% CI. Heterogeneity was checked by the chi square based Q test.

Figure 3. Begg’s funnel plot to examine publication bias for comparisons of Fok1 polymorphism (ff vs. Ff+FF).