Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
Department of Molecular Biology and Cancer Research, Azarbaijan Shahid Madani University, Tabriz, Iran.
PLoS One. 2019 Aug 6;14(8):e0220727. doi: 10.1371/journal.pone.0220727. eCollection 2019.
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 GA1CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA1CC and CA2GC 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 CA1GC haplotype was strongly identified as a breast cancer risk factor, and the GA1CC 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.
在癌症易感性基因中，TP53 是参与细胞周期调节的关键基因之一，因此极大地影响了乳腺癌的发生和发展。此外，WRAP53——一种天然的反义转录本——调节 TP53 的转录，作为一种蛋白质，调节正常的细胞周期，从而导致乳腺癌的易感性。在这项研究中，我们旨在分析一个由四个 SNP 组成的单倍型，包括位于 TP53 和 WRAP53 基因 5' 区域的 rs1042522、rs17878362、rs2287499 和 rs2287498，在 118 名伊朗-阿塞拜疆患者和 110 名健康对照中进行分析。通过 SIFT、Polyphen2、Fanthmm、RNAsnp 和 SNP&GO 在线服务器进行了计算机研究。通过 Haploview 程序计算了每个标记组合的连锁不平衡（LD）和 D'。我们的结果表明，在研究人群中，GA1CC 单倍型最为常见。此外，没有观察到任何成对单倍型之间存在显著的 LD。GA1CC 和 CA2GC 单倍型与乳腺癌易感性显著相关。此外，计算机分析显示 rs2287499 和 rs1042522 分别对 WRAP53 和 P53 有负面影响。总之，CA1GC 单倍型被强烈确定为乳腺癌的危险因素，而 GA1CC 单倍型被认为是乳腺癌风险的保护因素。因此，这些标记物可能潜在地用作乳腺癌的分子预后和预测生物标志物。
