Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population

Abstract

The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA, essential for p53 stabilization and induction upon DNA damage. Single nucleotide polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which strengthens the role of WRAP53 in the pathogenesis of human malignancies. In fact, WRAP53 has been considered as a candidate cancer susceptibility gene. Accordingly, we performed a study to examine the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population. A case-control association study, including 206 cases and 203 controls from Iranian-Azeri population, was conducted. Genomic DNA was extracted from peripheral blood and tumor samples by salting-out method. SNP genotyping was carried out by polymerase chain reaction-based single-strand conformational polymorphism (PCR-SSCP) technique. The sequence variation of SSCP banding patterns was determined by sequencing. The collected data were analyzed through statistical package for the social sciences software, using Chi-square (χ (2)) or Fisher's exact tests, with a significance level of 0.05. No significant differences in the allele and genotype frequencies between cases and controls were detected. Similarly, no significant associations between genotypes and clinicopathological data were observed. Concisely, no significant overall associations between rs2287499 and breast cancer risk and prognosis were detected in the studied population. The rs2287499 SNP is not associated with breast cancer predisposition in Iranian-Azeri women; it also cannot be used as a molecular biomarker to predict breast cancer prognosis in Iranian-Azeri population.

Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma

“…3,5 As little research has been conducted on the additional functions of WRAP53 in lung cancer, especially lung adenocarcinoma, its role in this disease remains unclear. The overexpression of WRAP53 is now considered a biomarker for a variety of cancers, such as colorectal cancer, hepatocellular carcinoma, head and neck carcinomas, breast cancer, esophageal squamous cell carcinoma, and rectal cancer, 8,9,18–21 which is consistent with the evidence obtained in this study of high WRAP53 expression in lung-adenocarcinoma tumor tissues and cell lines. The prevalence of WRAP53 overexpression was found to be significantly higher in patients with tumors larger than 3.0 cm, which led us to infer that the expression of WRAP53 is associated with the tumor-growth ability of lung adenocarcinoma.…”

Novel insights into a treatment for aplastic anemia based on the advanced proliferation of bone marrow-derived mesenchymal stem cells induced by fibroblast growth factor 1

“…Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and UCA1 were found to be abnormally expressed in melanoma metastases ( 32 ). X-inactive specific transcript was identified as a biomarker for membranous nephropathy ( 33 ) and WD repeat containing, antisense to TP53 was considered as a candidate for a cancer susceptibility gene ( 34 ). The bi-functional lncRNA, steroid receptor activator RNA 1 was identified to be a component of the steroid receptor coactivator-1 acetyltransferase complex and indicated to be an epigenetic regulatory component ( 35 ).…”

Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer

“…In the TP53 gene, rs17880604, rs1042522, and rs17878362 polymorphisms were genotyped by RFLP-PCR, ARMS-PCR, and PCR with silver staining methods, respectively, as previously described [25]. The genotype of rs2287499 polymorphism in the WRAP53 gene was determined using SSCP-PCR as described by Bonab et al [27]. The WRAP53 rs2287498 polymorphism was genotyped by tetra-ARMS-PCR method.…”

“…Our goal in this study was to conduct a haplotype-based association analysis at the TP53 - WRAP53 locus in breast cancer. To do so, we analyzed the association between four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which refer to R72P substitution in exon 4 of TP53 [25], a 16 bp duplication in intron 3 of TP53 [26], a R68G substitution in the first exon of WRAP53 [27], and a WRAP53 Ex2+19 C>T polymorphism, respectively, in Iranian-Azeri women to validate the question of “whether this haplotype has a potential to be utilized as a prognostic biomarker for breast cancer or not”.…”