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

• Published in: Journal of genetics Vol. 97; no. 5; pp. 1185 - 1194
• Main Authors: Abdul aziz, Ahmad Aizat, MD Salleh, MD Salzihan, Mohamad, Ibtisam, Bhavaraju, Venkata Murali Krishna, Yahya, Maya Mazuwin, Zakaria, Andee Dzulkarnaen, Gan, Siew Hua, Ankathil, Ravindran
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.12.2018; Springer; Springer Nature B.V
• Subjects: Alleles; Animal Genetics and Genomics; Antineoplastic drugs; Antitumor agents; Biomarkers; Biomedical and Life Sciences; Biotransformation; Breast cancer; Cancer; Cancer patients; Care and treatment; Chemoresistance; Chemotherapy; Cytochrome P-450; Cytochrome P450; Ethylenediaminetetraacetic acid; Evolutionary Biology; Gene expression; Gene polymorphism; Genotyping; Haplotypes; Life Sciences; Medical research; Medicine, Experimental; Messenger RNA; Microbial Genetics and Genomics; Paraffin; Patients; Plant Genetics and Genomics; Polymerase chain reaction; Polymorphism; Research Article; Restriction fragment length polymorphism; Reverse transcription; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Xenobiotics; triple negative breast cancer; mRNA; cytochrome P450 family 1 subfamily B1; chemotherapy response; single-nucleotide polymorphisms
• ISSN: 0022-1333; 0973-7731
• DOI: 10.1007/s12041-018-1013-x

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.