|
Abstract
|
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 50 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 D0 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.
|