scholarly journals Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Fatima AlMutairi ◽  
Akbar Ali Khan Pathan ◽  
Mohammed Alanazi ◽  
Manal Shalaby ◽  
Huda A. Alabdulkarim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Structure ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Progression ◽  
In Silico ◽  
Breast Cancer Progression ◽  
Saudi Population ◽  
Repair Gene ◽  
Ape1 Asp148glu

Objective. The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population.Methods. We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays andin silicostructural as well as functional predictions.In silicostructural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation.Results. Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. Thein silicoanalysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk.Conclusion. Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.

scholarly journals In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

2015 ◽  
Vol 26 (1-2) ◽  
pp. 57-79 ◽  
Author(s):  
Darryl L. Hadsell ◽  
Louise A. Hadsell ◽  
Walter Olea ◽  
Monique Rijnkels ◽  
Chad J. Creighton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Qtl Mapping ◽  
In Silico ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Ductal Development

scholarly journals Molecular Docking Studies to Understand the Potential Role of Ginger Compounds (6-Gingerol and 6-Shogaol) on Anti-Angiogenic and Anti-Lymphangiogenic Mechanisms

2019 ◽  
Vol 12 (1) ◽  
pp. 61
Author(s):  
Santhoshi Rani Nanchari ◽  
Shyam Perugu ◽  
Vijayalakshmi Venkatesan
Keyword(s):  
Breast Cancer ◽  
Binding Affinity ◽  
Cancer Progression ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Breast Cancer Progression ◽  
Biologically Active ◽  
Neuropilin 1 ◽  
Angiopoietin 2

Background: 6-Gingerol and 6-Shogaol are novel biologically active phenol compounds isolated from rhizomes of Ginger (Zingiber officinale Roscoe), which has a potential role as anti-inflammatory, anti-oxidant and apoptotic. Till date there are no scientific reports on the functional properties of Ginger against the molecular mechanisms of angiogenesis, lymphangiogenesis, and metastasis. Hence, in the present study we have explored the feasibility of active ginger compounds (6-Gingerol and 6-Shogaol) to validate their molecular mechanisms on angiogenesis and lymphangiogenesis in breast cancer progression through in silico approach. Methodology: Studies have been targeted to find the interactions between selected protein receptors, which play a pivotal role in angiogenesis and lymphangiogenesis and ligands of Ginger compounds (6-Gingerol and 6-Shogaol) by using Accelrys discovery studio 2.5, followed by analysis of data. Results: Based on the in silico approaches, we found the best interactions between ginger compounds (6-Gingerol and 6-Shogaol) and targeted protein molecules as shown less than 3.10 A0H-bond distance to indicate higher binding affinity and stronger interactions and high docking scores. We demonstrate docking interactions of 6-Gingerol with the proteins involved in angiogenesis like VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B, Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3) and with the proteins involved in lymphangiogenesis such as VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ). Similarly, our data shows that 6-Shogaol also interacts with angiogenic specific proteins, like [VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B), Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)] and lymphangiogenesis [VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ)]. Discussion: In silico approaches suggest a stronger binding affinity between the ginger compounds (6-Gingerol and 6-Shogaol) and selected proteins critical in angiogenesis and lymphangiogenesis. The present study underlines the feasibility of neutraceuticals to target the pathways participating in breast cancer progression through neovascularization. Our results also advocate 6-Gingerol to be more potent inhibitor of lymphangiogenesis assessed by its binding efficacy with VEGF-C and NRP2 (4QDS) as compared against 6-Shogaol.

scholarly journals Matrix metalloproteinase-2 C(-1306)T promoter polymorphism and breast cancer risk in the Saudi population.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Hesham Mahmoud Saeed ◽  
Mohammad Saud Alanazi ◽  
Omair Alshahrani ◽  
Narasimha Reddy Parine ◽  
Huda Abdullah Alabdulkarim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Matrix Metalloproteinase ◽  
Cancer Patients ◽  
Promoter Polymorphism ◽  
Matrix Proteins ◽  
Matrix Metalloproteinase 2 ◽  
Saudi Population ◽  
Breast Cancer Patients

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), displayed a strikingly lower promoter activity with the T allele. In the present study, we investigate whether this MMP-2 SNP is associated with susceptibility to breast cancer in the Saudi population. Ninety breast cancer patients and 92 age matched controls were included in this study. TaqMan Allele Discrimination assay and DNA sequencing techniques were used for genotyping. The results showed that, the frequency of MMP-2 CC wild genotype was lower in breast cancer patients when compared with healthy controls (0.65 versus 0.79). The homozygous CC (OR=2, χ(2)=5.36, p=0.02) and heterozygous CT (OR=1.98, χ(2)=4.1, p=0.04) showing significantly high risk of breast cancer in the investigated group. In conclusion our data suggest that the MMP-2 C(-1306)T polymorphism may be associated with increased breast cancer risk in the Saudi population.

The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population

2016 ◽  
Vol 23 (3) ◽  
pp. 525-535 ◽  
Author(s):  
Mohammed Alanazi ◽  
Akbar Ali Khan Pathan ◽  
Jilani P. Shaik ◽  
Abdullah Alhadheq ◽  
Zahid Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Gene Polymorphism ◽  
Saudi Population

scholarly journals Microbial Alterations and Risk Factors of Breast Cancer: Connections and Mechanistic Insights

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1091 ◽  
Author(s):  
Sheetal Parida ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Risk Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Progression ◽  
Immune Modulation ◽  
Cancer Risk Factors ◽  
Microbial Dysbiosis ◽  
Breast Cancer Risk Factors

Breast cancer-related mortality remains high worldwide, despite tremendous advances in diagnostics and therapeutics; hence, the quest for better strategies for disease management, as well as the identification of modifiable risk factors, continues. With recent leaps in genomic technologies, microbiota have emerged as major players in most cancers, including breast cancer. Interestingly, microbial alterations have been observed with some of the established risk factors of breast cancer, such as obesity, aging and periodontal disease. Higher levels of estrogen, a risk factor for breast cancer that cross-talks with other risk factors such as alcohol intake, obesity, parity, breastfeeding, early menarche and late menopause, are also modulated by microbial dysbiosis. In this review, we discuss the association between known breast cancer risk factors and altered microbiota. An important question related to microbial dysbiosis and cancer is the underlying mechanisms by which alterations in microbiota can support cancer progression. To this end, we review the involvement of microbial metabolites as effector molecules, the modulation of the metabolism of xenobiotics, the induction of systemic immune modulation, and altered responses to therapy owing to microbial dysbiosis. Given the association of breast cancer risk factors with microbial dysbiosis and the multitude of mechanisms altered by dysbiotic microbiota, an impaired microbiome is, in itself, an important risk factor.

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