Five Common Functional Polymorphisms in microRNAs and Susceptibility to Breast Cancer: An Updated Meta-Analysis

microRNAs (miRNA) play a key role in the pathogenesis of breast cancer (BC) as regulators of tumor-associated genes, and understanding their polymorphisms is critical to the control of breast carcinogenesis. Thus, the present study explored the association between five common functional polymorphisms in miRNAs (i.e., miRNA-196a2C>T, rs11614913; miRNA-146aG>C, rs2910164; miRNA-423C>A, rs6505162; miRNA-608G>C, rs4919510; miRNA-27aC>T, rs895819) and the risk of BC.

Meta-analyses were performed on 31 studies, including 14,677 BC patients and 16,143 cancer-free controls. Fourteen studies with 6147 cases and 5820 controls were analyzed for rs2910164, seventeen studies with 7021 cases and 8186 controls were analyzed for rs11614913, seven studies with 1891 (3390) cases and 2239 (5485) controls were analyzed for rs6505162 and rs4919510, respectively, and nine studies with 4499 cases and 5434 controls were analyzed for rs895819. Odds ratios (ORs) and 95% confidence intervals (CIs) were adopted to estimate BC risk. Subgroup analyses were performed for ethnicity. Because there was one study with mixed ethnicities, 16 studies were used in the analysis of Caucasian groups, and 16 studies were used for the Asian group.

Meta-analysis showed that rs895819 correlated with reduced BC risk in three genotypic models: allele (Caucasian: OR = 0.89, 95% CI = 0.82-0.97, p = 0.008; Total: OR = 0.93, 95% CI = 0.87-0.99, p = 0.03), recessive (Caucasian: OR = 0.85, 95% CI = 0.77-0.94, p = 0.002; Total: OR = 0.92, 95% CI = 0.85-0.99, p = 0.04), and dominant (Total: OR = 0.87, 95% CI = 0.77-0.99, p = 0.04). Of note, a significant publication bias for rs895819 was observed in the dominant model. Unexpectedly, the other four polymorphisms were not associated with BC risk in any of the models.

The present study indicates that only the rs895819 polymorphism was associated with BC risk.