miR-485-5p binding site SNP rs8752 in HPGD gene is associated with breast cancer risk

PLoS One. 2014 Jul 8;9(7):e102093. doi: 10.1371/journal.pone.0102093. eCollection 2014.

Abstract

Background: Single 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.

Methods: We 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.

Results: In 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.

Conclusion: Through 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Binding Sites
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / genetics*
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA Interference
  • Risk Factors

Substances

  • 3' Untranslated Regions
  • MIRN485 microRNA, human
  • MicroRNAs
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase

Grants and funding

This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) in China (IRT1076), the National Key Scientific and Technological Project (2011ZX09307-001-04), and the National Natural Science Foundation of China (No. 81172762). The tissue bank is jointly supported by the Tianjin Cancer Institute and Hospital and the U.S. National Foundation for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.