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

  • Epidemiology
  • Published:
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Abstract

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.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

ER+:

Estrogen receptor-positive

ER−:

Estrogen receptor-negative

GWAS:

Genome-wide association study

HWE:

Hardy–Weinberg equilibrium

LD:

Linkage disequilibrium

MAF:

Minor allele frequency

miRNA:

MicroRNA

OR:

Odds ratio

PR+:

Progesterone receptor-positive

PR−:

Progesterone receptor-negative

SNP:

Single nucleotide polymorphism

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Acknowledgments

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

None.

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Authors and Affiliations

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

    Hyuna Sung, Ji-Yeob Choi, Sue K. Park & Daehee Kang

  2. Department of Environmental Health, Korea National Open University, Seoul, Korea

    Kyoung-Mu Lee

  3. Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea

    Sohee Han, Ji-Young Lee, Sue K. Park, Keun-Young Yoo & Daehee Kang

  4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Lian Li, Sue K. Park, Dong-Young Noh & Daehee Kang

  5. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

    Dong-Young Noh

  6. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Sei-Hyun Ahn

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  1. Hyuna Sung
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  2. Kyoung-Mu Lee
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  10. Sei-Hyun Ahn
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Correspondence to Daehee Kang.

Electronic supplementary material

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Supplementary Table 1

The distributions of selected haplotypes in miRNA biogenesis pathway genes and breast cancer risks in postmenopausal women. (DOC 54 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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Sung, H., Lee, KM., Choi, JY. et al. Common genetic polymorphisms of microRNA biogenesis pathway genes and risk of breast cancer: a case–control study in Korea. Breast Cancer Res Treat 130, 939–951 (2011). https://doi.org/10.1007/s10549-011-1656-2

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