RESUMEN
MicroRNAs are key regulators of various fundamental biological processes and, although representing only a small portion of the genome, they regulate a much larger population of target genes. Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23 nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis and invasion. MicroRNA targeting is mostly achieved through specific base-pairing interactions between the 5' end ('seed' region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR diminish mRNA stability. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. Calin and Croce were the first to demonstrate a connection between microRNAs and increased risk of developing cancer, and meanwhile the role of microRNAs in carcinogenesis has definitively been evidenced. It needs to be considered that the complex mechanism of gene regulation by microRNAs is profoundly influenced by variation in gene sequence (polymorphisms) of the target sites. Thus, individual variability could cause patients to present differential risks regarding several diseases. Aiming to provide a critical overview of miRNA dysregulation in cancer, this article reviews the growing number of studies that have shown the importance of these small molecules and how these microRNAs can affect or be affected by genetic and epigenetic mechanisms.
RESUMEN
Due to the conflicting results regarding the association between breast cancer and the GSTM1 null mutation, our aim was to research this association in a Brazilian population and correlations with smoking, reproductive history and several clinical pathologies. A case-control study was performed on 105 women with breast cancer and 278 controls. Extraction of DNA was accomplished according to the protocol of the GFX kit and polymorphism analysis by the PCR technique. The control and experimental groups were compared and statistical analysis assessed by X2 or Fisher's exact test. The deletion in the GSTM1 gene in the breast cancer group had a prevalence of 32 (30.4%) individuals with the presence of null mutation. In the control group, the null mutation was present in 104 (37.4%) women. Upon comparison of the two groups, no statistically significant difference of the GSTM1 gene was observed, with an odds ratio (OR) of 0.74, 95%, confidence interval (CI) 0.45 - 1.20, p = 0.277. The results conclusively show that single gene GSTM1 polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, in this study no correlation was found between GSTs and smoking, reproductive history and several clinical pathologies with respect to cancer risk.