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 Ankathil

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    5 Citations (Scopus)

    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 embedded blocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326 C > 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.

    Original languageEnglish
    Pages (from-to)1185-1194
    Number of pages10
    JournalJournal of Genetics
    Volume97
    Issue number5
    DOIs
    Publication statusPublished - Dec 2018

    Keywords

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

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