1. Integrative Approach Detected Association between Genetic Variants of microRNA Binding Sites of TLRs Pathway Genes and OSCC Susceptibility in Chinese Han Population
- Author
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Yun Wang, Chongkui Sun, Taiwen Li, Jing Li, Hao Xu, Xin Zeng, Qianming Chen, Yu Zhou, Longjiang Li, Hongxia Dan, Lu Jiang, and Ga Liao
- Subjects
Untranslated region ,Male ,lcsh:Medicine ,Cell Signaling ,Genotype ,Molecular Cell Biology ,Medicine and Health Sciences ,Ethnicity ,lcsh:Science ,Genetics ,Mouth neoplasm ,Multidisciplinary ,Cancer Risk Factors ,Toll-Like Receptors ,Squamous Cell Carcinomas ,Genomics ,Middle Aged ,Oncology ,Carcinoma, Squamous Cell ,Female ,Mouth Neoplasms ,Research Article ,Biotechnology ,Signal Transduction ,Genetic Causes of Cancer ,Single-nucleotide polymorphism ,Biology ,Carcinomas ,Polymorphism, Single Nucleotide ,Head and Neck Squamous Cell Carcinoma ,Asian People ,Genetic variation ,microRNA ,SNP ,Humans ,Genetic Predisposition to Disease ,Genotyping ,Genetic Association Studies ,Oncogenic Signaling ,Evolutionary Biology ,Binding Sites ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,Cancers and Neoplasms ,Human Genetics ,Cell Biology ,stomatognathic diseases ,MicroRNAs ,Genetic Polymorphism ,lcsh:Q ,Population Genetics - Abstract
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.
- Published
- 2014