چکیده
|
p53 plays an important role in genome integrity and controls cell proliferation, induces cell cycle arrest, apoptosis, and DNA repair. Various lncRNAs, proteins, and small molecules can influence its activity. WRAP53, which lies in the opposite direction of TP53 on the opposite strand with 5′-5′ overlapping fashion, expressing three different transcripts with three alternative start exons. Based on informative values of SNPs in disease incident, studying gene polymorphism might help us to find a prognostic and therapeutic marker. Polymorphisms of TP53 as a major tumor suppressor gene and its overlapping gene, WRAP53, as an important protein in Cajal bodies trafficking have been shown to be associated with various cancer susceptibility. In this study, we assess the association of TP53 at codon 72 (R72P), which is a proline-to-arginine substitution, and WRAP53 at codon 68 (R68G), which is a Glycine-to-arginine substitution, with breast cancer susceptibility individuallyandasahaplotypeinthenorth-westofIranpopulation.Wegenotypedtwomentionedpolymorphisms in 206 cases of breast cancer and 180 controls with PCR-ARMS and PCR-SSCP methods. The results showed no statistically significant correlation of studied variants with breast cancer susceptibility and for the first time, we showed that the haplotype of these two SNPs (R72G68 genotype) has a significant difference (p-value=0.02) associated with breast cancer in these patients. In conclusion, the polymorphisms of TP53 at codon 72 and WRAP53 at codon 68 and their haplotype may confer an increased risk of breast cancer in the assessed population.
|