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Tesi etd-11172015-220239

Thesis type
Tesi di laurea magistrale
email address
Identification of polymorphic miRNA-binding sites associated with the risk of multiple myeloma
Corso di studi
relatore Prof.ssa Gemignani, Federica
Parole chiave
  • 3'-UTR
  • miRSNP
  • binding
  • binding energy
  • cancer
  • miRNA
  • multiple myeloma
Data inizio appello
Riassunto analitico
Multiple myeloma (MM) is a hematological neoplasm that represents about 13% of all hematological malignancies. Several evidences have suggested the presence of genetic factors able to confer susceptibility to MM. <br>The presence of single-nucleotide polymorphisms (SNPs) within the 3’-untranslated regions of genes, named miRSNPs, could affect the binding between a microRNA and its target, with consequences on gene expression regulation. Considering the important role of miRNAs in cancer etiopathogenesis, it is hypothesized here that these miRSNPs could also affect the individual risk of MM.<br>In this context, we performed a case-control study on MM susceptibility selecting 6 miRSNPs based on conservation along the evolution, in genes acting in different pathways relevant for cancer risk.<br>Initially, through a candidate gene approach we selected 52 genes involved in many biological functions (apoptosis, B cell differentiation, bone resorption, immunoglobulin production) which are deregulated in this neoplastic disease. Within these genes we selected the most conserved miRSNPs and evaluated them, in a case-control study, in relation to MM susceptibility. The miRSNPs selected for this study were: rs12587 (KRAS), rs10434 (VEGFA), rs1126772 (SPP1), rs11047885 (CASC1), rs3024496 (IL10), rs12211228 (IRF4). <br>The results provides evidence that carriers of the allele A (A/G+A/A) of rs3024496 show 26% higher risk of developing MM compared to the G/G individuals (OR: 1.26, C.I: 1.09-1.45, p-value: 0.001) in unadjusted dominant analysis. Moreover, both the heterozygotes (AG) and homozygotes (AA) have been associated with and increased risk of MM in unadjusted co-dominant model (OR = 1.24; 95% C.I. = 1.07 – 1.45; p-value = 0.004 and OR = 1.28; 95% C.I. = 1.09 – 1.51; p-value = 0.002) and a further analysis unveiled the presence of a trend both for unadjusted (p-value = 0.0047) and adjusted data (p-value =0.0047).<br>Thus, we can conclude that genetic variation on miRNA-binding site in IL10 could play an important role in etiology of MM cancer, even if further investigation are needed.<br>