Abstract
BackgroundMicroRNAs (miRNAs) are important small non-coding RNA molecules that regulate gene expression in cellular processes related to the pathogenesis of cancer. Genetic variation in miRNA genes could impact their synthesis and cellular effects and single nucleotide polymorphisms (SNPs) are one example of genetic variants studied in relation to breast cancer. Studies aimed at identifying miRNA SNPs (miR-SNPs) associated with breast malignancies could lead towards further understanding of the disease and to develop clinical applications for early diagnosis and treatment.MethodsWe genotyped a panel of 24 miR-SNPs using multiplex PCR and chip-based matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) analysis in two Caucasian breast cancer case control populations (Primary population: 173 cases and 187 controls and secondary population: 679 cases and 301 controls). Association to breast cancer susceptibility was determined using chi-square (X2) and odds ratio (OR) analysis.ResultsStatistical analysis showed six miR-SNPs to be non-polymorphic and twelve of our selected miR-SNPs to have no association with breast cancer risk. However, we were able to show association between rs353291 (located in MIR145) and the risk of developing breast cancer in two independent case control cohorts (p = 0.041 and p = 0.023).ConclusionsOur study is the first to report an association between a miR-SNP in MIR145 and breast cancer risk in individuals of Caucasian background. This finding requires further validation through genotyping of larger cohorts or in individuals of different ethnicities to determine the potential significance of this finding as well as studies aimed to determine functional significance.
Highlights
MicroRNAs are important small non-coding Ribonucleic Acid (RNA) molecules that regulate gene expression in cellular processes related to the pathogenesis of cancer
Analysis of single nucleotide polymorphisms in well-defined case control cohorts has provided information on MicroRNA single nucleotide polymorphism (miR-Single nucleotide polymorphisms (SNP)) involved in the pathophysiology of different types of cancer including breast cancer [25,26,27, 29,30,31,32,33]
We selected a panel of 24 miR-SNPs related to 9 miRNA genes previously identified to play a role in breast cancer to genotype in our Australian Caucasian breast cancer case control populations
Summary
MicroRNAs (miRNAs) are important small non-coding RNA molecules that regulate gene expression in cellular processes related to the pathogenesis of cancer. Single nucleotide polymorphisms (SNPs) in miRNA genes (miR-SNPs) are one example of point mutation (albeit one occurring in the past) that could affect miRNA function in one of three possible ways: altering transcription of the primary miRNA transcript; processing of the pri-miRNA and pre-miRNA and; through their effects on modulation of miRNA-mRNA interactions [20,21,22,23]. In genetic association analysis of Caucasian populations and functional studies in breast cancer cell lines performed by Hoffman et al the presence of SNP in MIR196A2 rs11614913 was significantly associated with reduced risk of breast cancer, as well as less efficient processing of MIR196A2 and reduced capacity to regulate target genes, indicating additional factors may be at work in this SNP’s effect on breast cancer [30]. Rs2910164, a miR-SNP located in the 3p strand of MIR146A, was found to be associated with a younger age of diagnosis in familial breast cancer for BRCA1 mutation carriers [33]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
