Chacon-Cortes Diego, Smith Robert A, Lea Rodney A, Youl Philippa H, Griffiths Lyn R
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, 4059, QLD, Australia.
Tumour Biol. 2015 Jul;36(7):5369-76. doi: 10.1007/s13277-015-3200-1. Epub 2015 Feb 14.
Breast cancer incidence and mortality rates are increasing despite our current knowledge on the disease. Ninety-five percent of breast cancer cases correspond to sporadic forms of the disease and are believed to involve an interaction between environmental and genetic determinants. The microRNA 17-92 cluster host gene (MIR17HG) has been shown to regulate expression of genes involved in breast cancer development and progression. Study of single-nucleotide polymorphisms (SNPs) located in this cluster gene could help provide a further understanding of its role in breast cancer. Therefore, this study investigated six SNPs in the MIR17HG using two independent Australian Caucasian case-control populations (GRC-BC and GU-CCQ BB populations) to determine association to breast cancer susceptibility. Genotyping was undertaken using chip-based matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry (MS). We found significant association between rs4824505 and breast cancer at the allelic level in both study cohorts (GRC-BC p = 0.01 and GU-CCQ BB p = 0.03). Furthermore, haplotypic analysis of results from our combined population determined a significant association between rs4824505/rs7336610 and breast cancer susceptibility (p = 5 × 10(-4)). Our study is the first to show that the A allele of rs4824505 and the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development. However, definitive validation of this finding requires larger cohorts or populations in different ethnical backgrounds. Finally, functional studies of these SNPs could provide a deeper understanding of the role that MIR17HG plays in the pathophysiology of breast cancer.
尽管我们目前对乳腺癌已有一定认识，但乳腺癌的发病率和死亡率仍在上升。95%的乳腺癌病例属于散发性疾病，据信涉及环境因素与遗传因素之间的相互作用。微小RNA 17 - 92簇宿主基因（MIR17HG）已被证明可调节参与乳腺癌发生和发展的基因表达。对该簇基因中单个核苷酸多态性（SNP）的研究有助于进一步了解其在乳腺癌中的作用。因此，本研究使用两个独立的澳大利亚白种人病例对照群体（GRC - BC和GU - CCQ BB群体）对MIR17HG中的六个SNP进行了研究，以确定其与乳腺癌易感性的关联。基因分型采用基于芯片的基质辅助激光解吸电离飞行时间（MALDI - TOF）质谱法（MS）。我们发现，在两个研究队列中，rs4824505在等位基因水平上与乳腺癌存在显著关联（GRC - BC中p = 0.01，GU - CCQ BB中p = 0.03）。此外，对我们合并群体的结果进行单倍型分析发现，rs4824505/rs7336610与乳腺癌易感性之间存在显著关联（p = 5×10⁻⁴）。我们的研究首次表明，rs4824505的A等位基因以及rs4824505/rs7336610的AC单倍型与乳腺癌发生风险相关。然而，这一发现的最终验证需要在不同种族背景下的更大队列或群体中进行。最后，对这些SNP的功能研究可以更深入地了解MIR17HG在乳腺癌病理生理学中的作用。
