Combined Genotype Effects of TP53 and PAI-1 Polymorphisms in Breast Cancer Susceptibility: Multifactor Dimensionality Reduction and in silico Analysis

2021 ◽  
pp. 1-10
Author(s):  
Nasser Pouladi ◽  
Mojtaba Shavali ◽  
Sepehr Abdolahi
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Cancer Susceptibility ◽  
Parametric Method ◽  
Gene Interaction ◽  
Case Control ◽  
Synergistic Interaction ◽  
In Silico Studies ◽  
Pai 1 ◽  
Genotype Effects

Introduction: Breast cancer is a heterogeneous and multifactorial disease. TP53 and PAI-1 as important tumor suppressor genes are involved in the development, invasion, and metastasis of many cancers. This study’s objective was to demonstrate the combined genotype effects of these 2 genes by investigating their single nucleotide polymorphisms. Methods: In this case-control study, 200 individuals with breast cancer and 179 healthy individuals were studied. The genotypes were determined using the tetra-ARMS method. For data analysis, MDR, online javstat statistics package, and SPSS v.24 software were used. Also, in silico studies on the estimated effects of each of these polymorphisms were performed. Results: We showed a novel gene-gene interaction of these 2 genes and demonstrated a strong synergistic interaction for TP53/PAI-1, moderate synergistic interaction for PAI-1/age, and correlation for TP53/age. On the other hand, there was no association between the allelic and genotype frequency alone and in combination, with case-control status, using the parametric method, between TP53 and PAI-1. Discussion/Conclusion: Our findings suggest that the polymorphism of codon 72 of the TP53 gene was significantly associated with tumor stage (p < 0.023). In conclusion, we showed a gene-gene interaction between TP53 and PAI-1, in combination, using the MDR method.

Design, Synthesis, In Vitro and In Silico Studies of Some Novel Triazoles as Anticancer Agents for Breast Cancer

2021 ◽  
pp. 131198
Author(s):  
Derya Osmaniye ◽  
Begum Nurpelin Saglik ◽  
Serkan Levent ◽  
Sinem Ilgın ◽  
Yusuf Ozkay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
In Silico ◽  
Design Synthesis ◽  
In Silico Studies

scholarly journals Single Nucleotide Polymorphism in hsa-mir-196a-2 and Breast Cancer Risk: A Case Control Study

2011 ◽  
Vol 14 (5) ◽  
pp. 417-421 ◽  
Author(s):  
Dominik J. Jedlinski ◽  
Plamena N. Gabrovska ◽  
Stephen R. Weinstein ◽  
Robert A. Smith ◽  
Lyn R. Griffiths
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Case Control ◽  
Cancer Tissue ◽  
Transcriptional Level ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

scholarly journals Genetic Variants in the Promoter Region of miR-10b and the Risk of Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jiaping Chen ◽  
Yue Jiang ◽  
Jing Zhou ◽  
Sijun Liu ◽  
Yayun Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
In Silico ◽  
Promoter Region ◽  
Cancer Susceptibility ◽  
Chinese Women ◽  
Close Association ◽  
Breast Cancer Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Variants in microRNA genes may affect their expression by interfering with the microRNA maturation process and may substantially contribute to the risk of breast cancer. Recent studies have identified miR-10b as an interesting candidate because of its close association with the metastatic behavior of breast cancer. However, the roles of miR-10b-related single nucleotide polymorphisms in breast cancer susceptibility remain unclear. This case-control study evaluated the associations between variants in the upstream transcription regulation region of miR-10b and the risk of breast cancer among Chinese women. Seven potentially functional SNPs were investigated using genotyping assays. The potential biological functions of the identified positive SNPs were further evaluated using in silico databases. We found that rs4078756, which was located at the promoter region of miR-10b, was significantly associated with breast cancer risk (rs4078756 AG/GG versus AA, adjusted odds ratio: 1.17, 95% confidence interval: 1.02–1.35). The other six single nucleotide polymorphisms exhibited negative associations. Based on the in silico prediction, rs4078756 potentially regulated miR-10b expression through promoter activation or repression. These findings indicate that a potentially functional SNP (rs4078756) in the promoter region of miR-10b may contribute to breast cancer susceptibility among Chinese women.

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