Abstract
Toll-like receptor (TLR4) 4 is present in numerous cell types and serves as the first point of defense in the innate immune system. Single-nucleotide polymorphisms (SNPs) are present in a number TLR genes and have been associated with various infection and inflammation disorders. Asp299Gly and Thr399Ile, TLR4 SNPs, are associated with tumor progression. In the present study, cases of ovarian cancer were analyzed with regards to Asp299Gly and Thr399Ile of the TLR4 gene. Genotype analysis was performed using DNA from tissue samples from stage I–IV patients with ovarian cancer. DNA from tissue samples was extracted and analyzed by a pyrosequencing method following multiplex polymerase chain reaction. The genotypes of these SNPs were analyzed in the present study in a population of 105 patients, with different types of ovarian cancer, between 2004 and 2012. The allele frequencies for TLR4 Asp299Gly identified in this population were 1.00 (A) and 0.00 (G); for TLR4 Thr399Ile the allele frequencies were; 1.00 (C) and 0.00 (T). For TLR4 Asp299Gly the observed genotype frequency was 1.00 (AA), 0.00 (AG) and 0.0 (GG). In TLR4 Thr399Ile the observed genotype frequencies were 1.00 (CC), 0.00 (CT) and 0.00 (TT). TLR4 Asp299Gly and Thr399Ile alleles were not detected in the patients. These results indicated that the TLR4 299Gly and 399Ile alleles were exhibited at a lower frequency in the ovarian cancer patients that were examined.
Highlights
Chronic infection and inflammation are important epigenetic factors contributing to tumorigenensis and tumor progession [1]
Pyrosequencing was conducted for the simultaneous detection of Asp299Gly and Thr399Ile in the Toll‐like receptor 4 (TLR4) gene
The allele frequencies for TLR4 Asp299Gly identified in this population were 1.00 (A) and 0.00 (G); for TLR4 Thr399Ile the allele frequencies were, 1.00 (C) and 0.00 (T)
Summary
Chronic infection and inflammation are important epigenetic factors contributing to tumorigenensis and tumor progession [1]. Toll-like receptors (TLRs) are important pattern recognition receptors expressed by immune cells. Toll‐like receptor 4 (TLR4) expression has been investigated in tumor cells or cell lines, including gastric carcinoma, extranodal marginal zone B‐cell lymphomas, pituitary epithelial tumor cell lines, hepatocellular carcinoma cells, colon cancer cells and human prostate epithelial PC3 cells. The TLR4 single‐nucleotide polymorphisms (SNPs), Asp299 and Thr399, have been reported to be involved in inflammation and cancer [2,3]. It was hypothesized that the presence of TLR4 variants may lead to the development of ovarian cancer. The relevance of TLR4 SNPs, Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are investigated in 105 ovarian cancer patients retrospectively with an extended follow‐up and complete representative adjuvant therapy (chemotherapy with or without surgical treatment)
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