Abstract
BackgroundCytochrome P450 3A enzymes exhibit a variety of physiological roles and have been reported to be the most predominant enzymes involved in drugs metabolism. Single nucleotide polymorphisms (SNPs) in the genes that code for these enzymes may result in functional changes that affect enzyme activity. CYP3A4 is an important enzyme in the metabolism of many important drugs used in the treatment of breast cancer.MethodsA total of 94 post-menopausal breast cancer patients were recruited for the study and their DNA was isolated for polymerase chain reaction (PCR). The primers were designed using Primer3 software with primer specificities checked via the Basic Local Alignment Tool (BLAST) database. The primer specificity, functionality and annealing temperature were first investigated using uniplex PCR protocols, followed by a single multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The digested amplification fragments were analysed by gel electrophoresis and subsequently validated by sequencing.ResultsA multiplex PCR-RFLP method was successfully developed for simultaneous detection of CYP3A4*4, CYP3A4*18B and CYP3A4*22 in a population of post-menopausal breast cancer patients.ConclusionThe technique is simple, cost-effective, time-saving and can be routinely applied in the identification of SNPs and determination of allelic and genotypic frequencies of CYP3A4*4, CYP3A4*18B and CYP3A4*22.
Highlights
The cytochromes P450 or commonly known as CYPs P450, are of a superfamily of hemebinding enzymes with various physiological roles [1]
A significant pool of data suggests that genetic variation in the CYP3A4 gene results in functional changes that may significantly affect its activity leading to serious consequences for patients [3, 4]
A similar study reported that breast cancer patients harbouring CYP3A4*22 had lower tendency to develop of tamoxifen-associated hot flashes [12]
Summary
The cytochromes P450 or commonly known as CYPs P450, are of a superfamily of hemebinding enzymes with various physiological roles [1]. The cytochrome P450 3A (CYP3A4) is believed to be the most predominant enzyme involved in metabolism of drugs used in clinical practice [2]. A significant pool of data suggests that genetic variation in the CYP3A4 gene results in functional changes that may significantly affect its activity leading to serious consequences for patients [3, 4]. CYP3A4 plays a key role in the metabolism of important drugs used in breast cancer treatment which include anastrozole [5], letrozole [6], exemestane [7], tamoxifen [8], cyclophosphamide, paclitaxel and docetaxel. Cytochrome P450 3A enzymes exhibit a variety of physiological roles and have been reported to be the most predominant enzymes involved in drugs metabolism. CYP3A4 is an important enzyme in the metabolism of many important drugs used in the treatment of breast cancer
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