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Oral squamous cell carcinoma (OSCC) is a leading malignancy worldwide; the overall 5-year survival rate is approximately 50%. A variety of proteins in Toll-like receptors (TLRs) pathway have been related with the risk of OSCC. However, the influence of genetic variations in TLRs pathway genes on OSCC susceptibility is unclear. Previous studies mainly focused on the coding region of genes, while the UTR region remains unstudied. In the current study, a bioinformatics approach was performed to select candidate single nucleotide polymorphisms (SNPs) on microRNA binding sites of TLRs pathway genes related with OSCC. After screening 90 OSCC related TLRs pathway genes, 16 SNPs were selected for genotyping. We found that rs5030486, the polymorphisms on 3' UTR of TRAF6, was significantly associated with OSCC risk. AG genotype of TRAF6 was strongly associated with a decreased risk of OSCC (OR = 0.252; 95% CI = 0.106, 0.598; p = 0.001). In addition, AG genotype was also related with a reduced risk of OSCC progression both in univariable analysis (HR = 0.303, 95% CI = 0.092, 0.995) and multivariable analysis (HR = 0.272, 95% CI = 0.082, 0.903). Furthermore, after detecting the mRNA expression level of TRAF6 in 24 OSCC patients, we found that TRAF6 expression level was significantly different between patients carrying different genotypes at locus rs5030486 (p = 0.013), indicating that rs5030486 of TRAF6 might contribute to OSCC risk by altering TRAF6 expression level. In general, these data indicated that SNP rs5030486 could be a potential bio-marker for OSCC risk and our results might provide new insights into the association of polymorphisms within the non-coding area of genes with cancers.
Pubmed ID: 24999832
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Database as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.
View all literature mentionsDatabase of naturally occurring DNA variations in microRNA (miRNA) seed regions and miRNA target sites. MicroRNAs pair to the transcripts of protein-coding genes and cause translational repression or mRNA destabilization. SNPs and INDELs in miRNAs and their target sites may affect miRNA-mRNA interaction, and hence affect miRNA-mediated gene repression. The PolymiRTS database was created by scanning 3'UTRs of mRNAs in human and mouse for SNPs and INDELs in miRNA target sites. Then, the potential downstream effects of these polymorphisms on gene expression and higher-order phenotypes are identified. Specifically, genes containing PolymiRTSs, cis-acting expression QTLs, and physiological QTLs in mouse and the results of genome-wide association studies (GWAS) of human traits and diseases are linked in the database. The PolymiRTS database also includes polymorphisms in target sites that have been supported by a variety of experimental methods and polymorphisms in miRNA seed regions.
View all literature mentionsSoftware program that analyzes patterns of linkage disequilibrium (LD) between polymorphic sites in a locus, and bins the SNPs on the basis of a threshold level of LD as measured by r2. (entry from Genetic Analysis Software)
View all literature mentionsWeb tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.
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