Association of microRNA 17–92 cluster host gene (MIR17HG) polymorphisms with breast cancer
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.
KeywordsAssociation analysis Breast cancer Haplotype MicroRNA Single nucleotide polymorphisms (SNP)
This research was funded by research grants from the Griffith Health Institute, the Cancer Council Queensland and funding from the national Health and Medical Research Council. Blood samples from the Griffith University-Cancer Council Queensland Biobank were collected from patients enrolled in Cancer Council Queensland’s Breast Cancer Outcomes Study funded by a Cancer Australia grant (no. 1006339). Dr Youl is supported by an NHMRC Early Career Research Fellowship (no. 1054038). We thank Professor Suzanne K. Chambers for her assistance in the development of this project. In addition, this study used infrastructure provided by the Australian government EIF Super Science Funds as part of the Therapeutic Innovation Australia—Queensland node project.
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