Single-nucleotide polymorphism in microRNA-binding site of SULF1 target gene as a protective factor against the susceptibility to breast cancer: a case-control study

PURPOSE Numerous clinical studies have suggested that chemopreventive drugs for breast cancer such as tamoxifen and exemestane can effectively reduce the incidence of estrogen receptor (ER)-positive breast cancer. However, it remains unclear how to identify those who are susceptible to ER-positive breast cancer. Accordingly, there is a great demand for a probe into the predisposing factors so as to provide precise chemoprevention. Recent evidence has indicated that ERα expression can be regulated by microRNAs (miRNAs), such as miR-206, in breast cancer. We assumed that single-nucleotide polymorphisms (SNPs) in the miR-206-binding sites of the target genes may be associated with breast cancer susceptibility with different ER statuses. METHODS We genotyped the SNPs that reside in and around the miR-206-binding sites of two target genes - heparan sulfatase 1 (SULF1) and RPTOR-independent companion of mammalian target of rapamycin Complex 2 (RICTOR) - which were related to the progression or metastasis of breast cancer cells in 710 breast cancer patients and 294 controls by the matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to evaluate the potential association between the SNPs and breast cancer susceptibility. RESULTS For rs3802278, which is located in the 3'-untranslated region (3'-UTR) of SULF1, the frequency of the AA genotype was less in breast cancer patients than that in the controls as compared to that of the GG + GA genotype not only for ER-positive breast cancer patients (adjusted OR =0.663, P=0.032) but also for hormone receptor-positive breast cancer patients (adjusted OR =0.610, P=0.018). Besides, the frequency of the AA genotype was less than that of the GG genotype between the ER-positive breast cancer patients and the controls (adjusted OR =0.791, P=0.038). For rs66916453, which is located in the 3'-UTR of RICTOR, no significant difference was observed between the case and the control group for the genotypes or alleles (P>0.05). CONCLUSION The SNPs in the miRNA-binding sites within the 3'-UTR of SULF1 may serve as protective factors against the susceptibility to breast cancer, especially to ER-positive breast cancer in the Chinese population. These SNPs are promising candidate biomarkers to predict the susceptibility of breast cancer and guide the administration of targeted preventive endocrine therapy.