Abstract
Recently the functional variant of precursor form of microRNA-27a (miR-27a: rs895819; n.40A>G) has been related to several cancers including breast cancer (BC), albeit with conflicting evidence. The current updated meta-analysis aimed to explore the possible association between this variant and BC risk based on more stratification analysis, correlation with the clinico-pathological and prognostic parameters and including more recent publications. Searches were carried out in PubMed and other databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate BC risk. In silico analysis of the structural and functional impact of the studied variant was also executed.
A total of 12 eligible studies with 5441 BC patients and 6250 controls were enrolled. Overall analysis revealed no association between the rs895819 polymorphism and BC risk. However, on stratified analysis by ethnicity, a decreased risk was observed in the Caucasian population [OR (95% CI); G vs. A: 0.894 (0.823–0.970), AG vs. AA: 0.843 (0.753–0.943), and AG/GG vs. AA: 0.850 (0.763–0.947)]. Subgroup analysis revealed a protective effect of G variant in patients with familial BC [G vs. A: 0.89 (0.83–0.97)], among population-based subgroup [G vs. A: 0.92 (0.86, 0.98)], patients´ young age [G vs. A: 0.85 (0.78, 0.94)] and BRCA1/2 negative mutations [G vs. A: 0.89 (0.82, 0.96)]. No association with patients' age, pathological cancer type, or HER2 hormonal receptors was detected. However, patients with AG/GG genotypes were shown to be more likely to have tumor tissue with positive estrogen receptors under a dominant model (AG/GG vs. AA: OR = 1.59, 95% CI = 1.09–2.33). In conclusion overall miR-27a (rs895819) polymorphism was not associated with BC risk. However, the rs895819*G variant may confer protection against cancer in Caucasian and familial BC. Well-designed studies with larger cohorts in diverse ethnic populations are warranted.