SNPs within microRNA binding sites and the prognosis of breast cancer

Abstract

Single nucleotide polymorphisms (SNPs) within microRNA binding sites can affect the binding of microRNA to mRNA and regulate gene expression, thereby contributing to cancer prognosis. Here we performed a two-stage study of 2647 breast cancer patients to explore the association between SNPs within microRNA binding sites and breast cancer prognosis. In stage I, we genotyped 192 SNPs within microRNA binding sites using the Illumina Goldengate platform. In stage II, we validated SNPs associated with breast cancer prognosis in another dataset using the TaqMan platform. 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, 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 associated with poor survival of breast cancer (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 and lymph node-negative patients (P<0.05). The Leucine-rich repeat kinase 2 (LRRK2) rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population and may be used as a potential prognostic biomarker for breast cancer. • The LRRK2 rs10878441 CC genotype is associated with poor prognosis of breast cancer in a Chinese population. • Stratified analyses demonstrated that rs10878441 was related to breast cancer prognosis in grade II patients and lymph node-negative patients.