• Fulltext

       

        Click here to view fulltext PDF


      Permanent link:
      https://www.ias.ac.in/article/fulltext/jgen/097/05/1185-1194

    • Keywords

       

      triple negative breast cancer; cytochrome P450 family 1 subfamily B1; single-nucleotide polymorphisms; mRNA; chemotherapy response.

    • Abstract

       

      Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

    • Author Affiliations

       

      AHMAD AIZAT ABDUL AZIZ1 MD SALZIHAN MD SALLEH2 IBTISAM MOHAMAD3 VENKATA MURALI KRISHNA BHAVARAJU4 MAYA MAZUWIN YAHYA5 ANDEE DZULKARNAEN ZAKARIA5 SIEW HUA GAN6 RAVINDRAN ANKATHIL1

      1. Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
      2. Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
      3. Department of Pathology, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
      4. Adventist Oncology Center, Penang Adventist Hospital, Pulau Pinang, Malaysia
      5. Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
      6. Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia
    • Dates

       
  • Journal of Genetics | News

© 2017-2019 Indian Academy of Sciences, Bengaluru.