Background: Micro-RNAs (miRNAs or miRs) are small, non-coding sequences of RNA that function to negatively regulate gene expression and have been implicated as oncogenes and tumour suppressor genes in a range of different cancers. More recently, miRNA single nucleotide polymorphisms (miRSNPs) have been linked to the development of several cancers by potentially influencing miRNA networks. SNPs located in miRNA biogenesis genes, in precursor or mature regions, or in the 3’UTR binding sites of target genes, may all play a role as potential diagnostic biomarkers. To date, several miRSNPs have been identified in haematological malignancies with only a few identified in lymphoma.
Methodology: As few miRSNPs have been directly associated with lymphoma, we have developed a panel of miRSNPs related to cancer/lymphoma, identified using a comprehensive review of the current literature and databases, which will be examined via MassARRAY. 65 miRSNPs will be genotyped using multi-plex PCR and MALDI-TOF mass spectrometry analysis. We aim to perform a genetic association study on these polymorphisms and risk of NHL in our cohort of approximately 300 NHL cases and 150 cancer-free controls that are matched according to age, sex and ethnicity and for which genomic DNA has been extracted.
Expected Results: We hypothesise miRSNPs play a role in the development and heritable risk of NHL. As few miRSNPs have been identified in NHL to date, we have incorporated other cancer related miRSNPs into our assay design to determine if these are associated with lymphomagenesis. Where possible, we will correlate genetic association data with miRNA gene expression to determine if the detected miRSNPs function to influence miRNA levels in available matching FFPE lymph nodes.
Conclusion: The association of miRSNPs and cancer risk is a new field of research. This study aims to contribute to the gaps in knowledge regarding miRSNPs and susceptibility to NHL.