miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk

Abstract

BackgroundSingle nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China.MethodsWe performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set.ResultsIn stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant.ConclusionThrough a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.

Epigallocatechin‐3‐gallate inhibited cancer stem cell–like properties by targeting hsa‐mir‐485‐5p/RXRα in lung cancer

“…For instance, hsa‐mir‐485‐5p can reverse epithelial to mesenchymal transition and promote cisplatin‐induced cell death via targeting P21 (RAC1) activated kinase 1 (PAK1) in oral tongue squamous cell carcinoma . Hsa‐mir‐485‐5p–binding site single‐nucleotide polymorphism rs8752 in the 15‐hydroxyprostaglandin dehydrogenase (HPGD) gene is correlated with the risk of breast cancer . However, its cellular function in NSCLC is not clear.…”

“…40 Hsa-mir-485-5p-binding site single-nucleotide polymorphism rs8752 in the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene is correlated with the risk of breast cancer. 41 However, its cellular function in NSCLC is not clear. Consistent with the roles of hsa-mir-485-5p in other cancers, we found that hsa-mir-485-5p was decreased in serum samples from NSCLC patients and NSCLC cells.…”

Genomic alterations as mediators of miRNA dysregulation in ovarian cancer

“…In addition, RNAsnp (http://rth.dk/resources/ rnasnp/submit) is a web-based tool which enables the prediction of structural changes induced by SNPs (Sabarinathan et al, 2013). These freely available databases and tools may support the study of functional changes associated with miRNA variants and have supported several studies to date (He et al, 2014b;Li et al, 2014;Swart and Dandara, 2014). The Collaborative Oncological Gene-environment Study assessed the association of 767 MirSNPs and EOC risk in 18,174 EOC cases and 26,134 controls.…”

A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer

“…Afterward numerous investigations have revealed the SNPs within miRNA-binding region may contribute to cancer risk and outcomes by altering miRNA-mRNA binding affinities and miRNA-targeted gene expression [7, 8]. For example, He et al found that rs8752 located with miR-485-5p -binding site of HPGD gene was related to the risk of breast cancer [9]. Zhang et al found that miR-367 -binding site rs1044129 in RYR3 gene was associated with poor survival of patients with breast cancer [10].…”