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Open Access Research article

Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival

Hyuna Sung1, Sujee Jeon2, Kyoung-Mu Lee3, Sohee Han4, Minkyo Song1, Ji-Yeob Choi15, Sue K Park145, Keun-Young Yoo4, Dong-Young Noh56, Sei-Hyun Ahn7 and Daehee Kang145*

Author Affiliations

1 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, South Korea

3 Department of Environmental Health, Korea National Open University, Seoul, South Korea

4 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea

5 Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

6 Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea

7 Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea

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BMC Cancer 2012, 12:195  doi:10.1186/1471-2407-12-195

Published: 28 May 2012

Abstract

Background

Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown.

Methods

We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died.

Results

Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07).

Conclusions

Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

Keywords:
microRNA biogenesis pathway; Breast cancer; Survival; Single nucleotide polymorphism