Screening for the 3' UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential role in Pharmacogenomics

Revathidevi, Sundaramoorthy; Sudesh, Ravi; Vaishnavi, Varadharajan; Kaliyanasundaram, Muthukrishnan; MaryHelen, Kilyara George; Sukanya, Ganesan; Munirajan, Arasambattu Kannan

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자료유형: 학술저널

저자정보: Revathidevi, Sundaramoorthy (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) Sudesh, Ravi (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) Vaishnavi, Varadharajan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) Kaliyanasundaram, Muthukrishnan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) MaryHelen, Kilyara George (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) Sukanya, Ganesan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras) Munirajan, Arasambattu Kannan (Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제17권 제8호

발행연도: 2016.1

수록면: 3,971 - 3,977 (7page)

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Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

#Pregnane X receptor #3' UTR variation #MiRSNPs #drug metabolism #doxorubicin #cardiotoxicity

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