Association between SNPs within MicroRNA Binding Sites and the Prognosis of Breast Cancer

Abstract Background: Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to the prognosis of cancer. We performed this study to explore the association between SNPs within microRNA binding sites and the prognosis of breast cancer.Methods: We carried out a two-stage study including 2647 breast cancer patients, with a median follow-up of 68 months (range 0-159). In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs significantly associated with breast cancer prognosis in another dataset using the TaqMan platform. Survival times was calculated, and Kaplan-Meier curves and Cox regression model were used to analyze survival of breast cancer patients with different genotypes.Results: We identified 8 SNPs significantly associated with breast cancer prognosis in stage I (P<0.05), and only rs10878441 was statistically significant in stage II (AA vs CC: adjusted HR=2.21, 95% CI: 1.11-4.42, P=0.024). We combined the data from stage I and stage II, and found that, compared with rs10878441 AA genotype, CC genotype was significantly associated with poor survival of breast cancer (HR=1.69, 95% CI: 1.18-2.42, P=0.004; adjusted HR=2.19, 95% CI: 1.30-3.70, P=0.003). Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients (P<0.05).Conclusions: The LRKK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population, and it could be used as a potential prognostic biomarker for breast cancer. Further studies are warranted.