Journal of Genetics

, Volume 97, Issue 5, pp 1185–1194 | Cite as

Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

  • Ahmad Aizat Abdul aziz
  • MD Salzihan MD Salleh
  • Ibtisam Mohamad
  • Venkata Murali Krishna Bhavaraju
  • Maya Mazuwin Yahya
  • Andee Dzulkarnaen Zakaria
  • Siew Hua Gan
  • Ravindran AnkathilEmail author
Research Article


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 \(\hbox {C}{>}\hbox {G}\), 4326 \(\hbox {C}{>}\hbox {G}\) and 4360 \(\hbox {A}{>}\hbox {G}\), 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 embedded blocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326 \(\hbox {C}{>}\hbox {G}\) 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 good treatment 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.


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



This study was supported by Universiti Sains Malaysia, Research University Team (RUT) Grant (1001/PPSP/853005).


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Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Ahmad Aizat Abdul aziz
    • 1
  • MD Salzihan MD Salleh
    • 2
  • Ibtisam Mohamad
    • 3
  • Venkata Murali Krishna Bhavaraju
    • 4
  • Maya Mazuwin Yahya
    • 5
  • Andee Dzulkarnaen Zakaria
    • 5
  • Siew Hua Gan
    • 6
  • Ravindran Ankathil
    • 1
    Email author
  1. 1.Human Genome CentreUniversiti Sains MalaysiaKubang KerianMalaysia
  2. 2.Department of Pathology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia
  3. 3.Department of PathologyHospital Raja Perempuan Zainab IIKota BharuMalaysia
  4. 4.Adventist Oncology CenterPenang Adventist HospitalPulau PinangMalaysia
  5. 5.Department of Surgery, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia
  6. 6.PharmacyMonash University MalaysiaBandar SunwayMalaysia

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