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Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer
Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53—a natural antisense transcript—regulates TP53 transcription and, as a protein, modulates the nor...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684289/ https://www.ncbi.nlm.nih.gov/pubmed/31387111 http://dx.doi.org/10.1371/journal.pone.0220727 |
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author | Pouladi, Nasser Abdolahi, Sepehr Farajzadeh, Davoud Hosseinpour Feizi, Mohammad Ali |
author_facet | Pouladi, Nasser Abdolahi, Sepehr Farajzadeh, Davoud Hosseinpour Feizi, Mohammad Ali |
author_sort | Pouladi, Nasser |
collection | PubMed |
description | Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53—a natural antisense transcript—regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5′ regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D′ for each combination of the markers were calculated via the Haploview program. Our results showed that the GA(1)CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA(1)CC and CA(2)GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA(1)GC haplotype was strongly identified as a breast cancer risk factor, and the GA(1)CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer. |
format | Online Article Text |
id | pubmed-6684289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66842892019-08-15 Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer Pouladi, Nasser Abdolahi, Sepehr Farajzadeh, Davoud Hosseinpour Feizi, Mohammad Ali PLoS One Research Article Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53—a natural antisense transcript—regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5′ regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D′ for each combination of the markers were calculated via the Haploview program. Our results showed that the GA(1)CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA(1)CC and CA(2)GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA(1)GC haplotype was strongly identified as a breast cancer risk factor, and the GA(1)CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer. Public Library of Science 2019-08-06 /pmc/articles/PMC6684289/ /pubmed/31387111 http://dx.doi.org/10.1371/journal.pone.0220727 Text en © 2019 Pouladi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Pouladi, Nasser Abdolahi, Sepehr Farajzadeh, Davoud Hosseinpour Feizi, Mohammad Ali Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title_full | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title_fullStr | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title_full_unstemmed | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title_short | Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer |
title_sort | haplotype and linkage disequilibrium of tp53-wrap53 locus in iranian-azeri women with breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684289/ https://www.ncbi.nlm.nih.gov/pubmed/31387111 http://dx.doi.org/10.1371/journal.pone.0220727 |
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