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.
OBJECTIVE
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).


CONCLUSIONS
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.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Department of Gynecology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
Qiong
Q
Zhou
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Breast Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Yiwei
Y
Jiang
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Wenjin
W
Yin
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Breast Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Yaohui
Y
Wang
Breast Cancer Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Jinsong
J
Lu
SULF1; breast cancer susceptibility; miRNA; single-nucleotide polymorphism