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Screening for the 3 UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential role in Pharmacogenomics |
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| รหัสดีโอไอ | |
| Creator | 1. Sundaramoorthy Revathidevi 2. Ravi Sudesh; Varadharajan Vaishnavi; Muthukrishnan Kaliyanasundaram; Kilyara George MaryHelen; Ganesan Sukanya; Arasambattu Kannan Munirajan |
| Title | Screening for the 3 UTR Polymorphism of the PXR Gene in South Indian Breast Cancer Patients and its Potential role in Pharmacogenomics |
| Publisher | APJCP |
| Publication Year | 2559 |
| Journal Title | Asian Pacific Journal of Cancer Prevention |
| Journal Vol. | 17 |
| Journal No. | 8 |
| Page no. | 3971-3977 |
| Keyword | Pregnane X receptor ; 3 UTR variation ; MiRSNPs ; drug metabolism ; doxorubicin ; cardiotoxicity |
| Abstract | 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 3๊ UTR was ampli ed 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 3๊ 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 identi ed 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 identi ed in PXR 3๊ UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for inter- individual variability in treatment response and toxicity associated with chemotherapy. |
