Menopausal status could modify breast cancer risk associated with the fokI polymorphism in vitamin D receptor gene: a meta-analysis

The FokI polymorphism in vitamin D receptor (VDR) gene has been reported to influence the risk of breast cancer among females. However, the association between the FokI polymorphism and breast cancer risk could probably be interfered by menopausal status. Actually, there is inconsistent evidence about the association among premenopausal and postmenopausal women. A meta-analysis was conducted to precisely estimate the association between the FokI polymorphism and breast cancer risk stratified by menopausal status. Two eligible case-control studies involving 1,526 cases and 2,058 control subjects among premenopausal women and five eligible studies involving 7,738 cases and 10,453 control subjects among postmenopausal women were identified through searching PubMed, Web of Science, CNKI and CBM. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using a fixed-effect model or random-effect model based on the result of significant test for heterogeneity. The results showed that no overall significant breast cancer risk was found to be associated with any genetic contrast model of the FokI polymorphism among premenopausal women, while overall significant breast cancer risk was associated with the homozygous model (OR=1.106, 95% CI=1.011-1.211; PQ=0.153, I-2=40.3% for ff vs. FF) and the dominant model (OR=1.105, 95% CI=1.017-1.200; PQ=0.545, I-2=0.0% for ff vs. Ff+FF) of the FokI polymorphism among postmenopausal women, respectively. Begg's test and Egger's test for all genetic contrast models did not support the publication bias of the studies in postmenopausal women. Therefore, the VDR FokI polymorphism may represent a risk factor of breast cancer among postmenopausal women, whereas not among premenopausal women. More studies are warranted to evaluate the association of the FokI polymorphism with breast cancer risk stratified by menopausal status worldwide.