Correlation between P53 Arg72Pro and MDM4 gene rs4245739 polymorphisms in breast cancer

• Published in: Gene reports Vol. 20; p. 100785
• Main Authors: Pedram, Negar, Pouladi, Nasser, Feizi, Mohammad Ali Hosseinpour, Gavgani, Reyhaneh Ravanbakhsh, Asadi, Milad, Bornehdeli, Soghra, Sakhinia, Ebrahim
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2020
• Subjects: Breast cancer; MDM4; p53; Polymorphism; GWAS; OR; CI; 3′-UTR; Breast cancer; HRT; p53; FDR; SNPs; MDM2; T-ARMS-PCR; MDM4; Polymorphism
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2020.100785

MDM4 is a negative regulator of p53 tumor suppression pathway. Various studies reveal the fact that the rs4245739A>C polymorphism of MDM4 in 3′-untranslated region is targeted by miR-191 which leads to lower MDM4 expression. On the other hand, the importance of Arg72Pro polymorphism of p53 in breast cancer is proven. The aim of this study is to present the correlation between the aforementioned SNPs and the risk of breast cancer. The statistical society of the study includes 199 healthy women as the control group and 206 women suffering from breast cancer included from Turkish population of the East Azarbaijan. Alleles of both positions are detected through Tetra-ARMS PCR while SPSS and the SHEsis, online software was exerted for allele typing, genotyping, and haplotype analysis. Different alleles of both MDM4 rs4245739 and p53 Arg72Pro had no significant frequency in patients (P > 0.05). Furthermore, genotypes of neither MDM4 rs4245739 nor p53 Arg72Pro could increase or decrease the risk of breast cancer in patients compared to healthy women. Additionally, a significant factor affecting the risk of breast cancer is gene-gene interaction. The results of the ongoing study revealed that two genetic variants, MDM4 rs4245739 and p53 Arg72Pro polymorphisms, failed to be associated, individually and combined together, with the risk of breast cancer. However, additional well-designed studies on large populations are required to validate such an association. Various alleles of both SNPs had no significant frequency difference between patients and controls. Moreover, genotypes of neither MDM4 nor p53 were significantly distributed in women with breast cancer compared to the healthy controls. Meanwhile, haplotype analysis failed to be significant. Last but not least, all clinical manifestations, other than association between tumor size and MDM4 genotypes could not be correlated with either various alleles or genotypes. •MDM4 is a negative regulator of p53 tumor suppression pathway.•Genotypes of neither MDM4 nor p53 were significantly distributed in women with breast cancer compared to the healthy controls.•The results of the ongoing study revealed that two genetic variants, MDM4 rs4245739 and p53 Arg72Pro polymorphisms, failed to be associated, individually and combined together, with the risk of breast cancer.