Association of microRNA 17–92 cluster host gene (MIR17HG) polymorphisms with breast cancer

Abstract

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.

Association between polymorphisms of MIR17HG and risk of colorectal cancer in the Chinese Han population

“…It has been reported that the SNP rs9515692 in the promoter region of miR‐17‐92 was a protective factor for the susceptibility of systemic lupus erythematosus (Wang et al, ). Statistical analysis of allele frequencies in cases and controls in the Genomics Research Centre Breast Cancer population for rs7336610 showed significance; and haplotypic analysis of results showed that the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development (Chacon‐Cortes, Smith, Lea, Youl, & Griffiths, ). In this study, we investigated the association between the polymorphisms of MIR17HG and colorectal cancer risk in the Chinese Han population.…”

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

“…More importantly, we found that rs17735387 was related to the improved prognosis of glioma patients, particularly in low-grade glioma. Previously, rs7336610 was reported to be related to the risk of multiple myeloma and breast cancer, and rs17735387 not share any relationship with multiple myeloma risk and prognosis [14,22]. These results suggested that MIR17HG polymorphisms might have a different effect on the occurrence of different cancer types.…”

“…Research has shown that lncRNA MIR17HG was overexpressed in glioma and lncRNA MIR17HG knockdown inhibited glioma proliferation, migration, and invasion, suggesting lncRNA MIR17HG might facilitate glioma malignant progress [12]. Recent increasing evidence has indicated that the genetic polymorphisms of MIR17HG was associated with the occurrence of multiple tumors, such as lymphoma, colorectal cancer, breast cancer [13][14][15].…”

MIR17HG polymorphisms contribute to High altitude pulmonary edema susceptibility in Chinese Han people

“…Studies have confirmed that it participates in various growth and development processes such as cell proliferation and differentiation, angiogenesis, and plays an important role [10][11][12]. More and more studies have shown that the polymorphism of MIR17HG gene was associated with breast cancer [13], colorectal cancer [14], Multiple Myeloma [15].…”