Affiliation:
1. Atta-ur-Rahman School of Applied Biosciences (ASAB)/Assistant Professor/Healthcare Biotechnology, National University of Science and Technology, Islamabad, Pakistan
Abstract
BackgroundC-X-C chemokine ligand 12 (CXCL12) has important implications in breast cancer (BC) pathogenesis. It is selectively expressed on B and T lymphocytes and is involved in hematopoiesis, thymocyte trafficking, stem cell motility, neovascularization, and tumorigenesis. The single nucleotide polymorphism (SNP)rs1801157of CXCL12 gene has been found to be associated with higher risk of BC.MethodsOur study focuses on the genotypic and allelic distribution of SNP (rs1801157; G/A) in Pakistani population as well as its association with the clinico-pathological features. The association betweenrs1801157genotypes (G/A) and BC risks was assessed by a multivariate logistic regression (MLR) analysis. Genotyping was performed in both healthy individuals and patients of BC using PCR-restriction fragment length polymorphism (PCR-RFLP) method. Furthermore,in-silicoapproaches were adapted to investigate the association of CXCL12 and its receptor CXCR4 with genes/proteins involved in BC signalling.ResultsSignificant differences in allelic and genotypic distribution between BC patients and healthy individuals of genotype (G/G) and (A/G) (p < 0.05) were observed. The frequency of the allele G in the BC group (77%) was significantly higher as compared to control group (61%) (p = 0.01). The association of genotype GG with clinico-pathological features including age, stages of cancer and organ (lung, liver, bones and brain) metastasis (p > 0.05) was assessed. In a MLR analysis, a number of variables including age, weight of an individual, affected lymph nodes, hormonal status (estrogen and progesterone receptor), alcohol consumption and family history associated with the GG genotype (GG:AA, odds ratio (OR) = 1.30, 95% CI [1.06–1.60]) were found to be independent risk factors for BC. Ourin-vitroresults suggest that genotype GG is possibly increasing the risk of BC in Pakistani cohorts.in-silicoanalysis finds that CXCL12–CXCR4 is associated with an increased expression of PDZK1, PI3k and Akt which lead the breast tumor towards metastasis.ConclusionMultiple targets such as CXCL12, CXCR4, PDZK1, PI3k and Akt can be inhibited in combined strategies to treat BC metastasis.
Funder
National University of Science and Technology, Islamabad, Pakistan
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献