Breast Cancer Research and Treatment

, Volume 130, Issue 3, pp 939–951 | Cite as

Common genetic polymorphisms of microRNA biogenesis pathway genes and risk of breast cancer: a case–control study in Korea

  • Hyuna Sung
  • Kyoung-Mu Lee
  • Ji-Yeob Choi
  • Sohee Han
  • Ji-Young Lee
  • Lian Li
  • Sue K. Park
  • Keun-Young Yoo
  • Dong-Young Noh
  • Sei-Hyun Ahn
  • Daehee KangEmail author


Recent compelling evidence indicates that mutation, aberrant expression, and dysregulation of microRNA (miRNA) biogenesis are implicated in cancer development and progression. Based on the important role of miRNA biogenesis pathway in carcinogenesis, we hypothesized that genetic variations in this pathway genes may play a role as susceptibility factors for breast cancer. To test this hypothesis, we investigated the associations between 41 single nucleotide polymorphisms (SNPs) in 14 genes involved in miRNA biogenesis pathway and breast cancer risk in a case–control study of 559 Korean breast cancer cases and 567 controls frequency-matched by age. In all women, 3 SNPs (AGO1 rs595055, AGO2 rs3864659, and p68 rs1991401) were significantly associated with breast cancer risk. In stratified analysis by menopausal status, altered risk associations were observed for 7 SNPs in postmenopausal breast cancer. When subjects were grouped by the number of high-risk genotypes, we found a progressive increase in gene-dosage effect (P trend = 9.46E−7). The protective effects of AGO2 rs3864659 and HIWI rs11060845 were more pronounced in progesterone receptor-positive (PR+) cancer than in progesterone receptor-negative (PR−) cancer (odds ratio (OR), 0.50; 95% confidence interval (CI), 0.30–0.84 vs. OR, 0.94; 95% CI, 0.60–1.84; P heterogeneity = 0.04 and OR, 0.57; 95% CI, 0.37–0.88 vs. OR, 0.97; 95% CI, 0.65–1.44; P heterogeneity = 0.02, respectively), and the DROSHA rs644236 had stronger association with estrogen receptor-negative (ER−) cancer than for estrogen receptor-positive (ER+) cancer (OR, 1.39; 95% CI, 1.08–1.78 vs. OR, 1.05; 95% CI, 0.85–1.29; P heterogeneity = 0.04). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer risk, and the modifiable effects might be different according to the menopausal status and hormone receptor status.


MicroRNA biogenesis pathway Breast cancer Genetic susceptibility Single nucleotide polymorphism Hormone receptor status 



Body mass index


Confidence interval


Estrogen receptor-positive


Estrogen receptor-negative


Genome-wide association study


Hardy–Weinberg equilibrium


Linkage disequilibrium


Minor allele frequency




Odds ratio


Progesterone receptor-positive


Progesterone receptor-negative


Single nucleotide polymorphism



This research was supported by Basic Research Laboratory (BRL) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2010-0001200).

Conflict of interest


Supplementary material

10549_2011_1656_MOESM1_ESM.doc (54 kb)
Supplementary Table 1 The distributions of selected haplotypes in miRNA biogenesis pathway genes and breast cancer risks in postmenopausal women. (DOC 54 kb)
10549_2011_1656_MOESM2_ESM.docx (28 kb)
Supplementary Table for Editor Tagging efficiency: the proportion of common variants tagged by the tagSNPs in selected genes (DOCX 27 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Hyuna Sung
    • 1
  • Kyoung-Mu Lee
    • 2
  • Ji-Yeob Choi
    • 1
  • Sohee Han
    • 3
  • Ji-Young Lee
    • 3
  • Lian Li
    • 4
  • Sue K. Park
    • 1
    • 3
    • 4
  • Keun-Young Yoo
    • 3
  • Dong-Young Noh
    • 4
    • 5
  • Sei-Hyun Ahn
    • 6
  • Daehee Kang
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Biomedical SciencesSeoul National University College of MedicineSeoulKorea
  2. 2.Department of Environmental HealthKorea National Open UniversitySeoulKorea
  3. 3.Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
  4. 4.Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  5. 5.Department of SurgerySeoul National University College of MedicineSeoulKorea
  6. 6.Department of Surgery, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

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