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A Review Of The Rs1800716 Variant In Cyp2 D6 Is Associated With An Increased Double Endometrial Thickness In Postmenopausal Women On Tamoxifen

908 words - 4 pages

Introduction
The Journal article being referenced is focused on the correlation between the rs1800716 variant in CYP2D6 and double endometrial thickness in woman who are postmenopausal and taking tamoxifen for breast cancer1. A past study conducted in 2010, displayed woman who used tamoxifen had an increased risk of getting uterine sarcoma or endometrial cancer, this number turned out to be about 1 in 1,000 women per year2. Another study conducted in 2012 at the University of Tokyo called, Pharmacogenomics of Tamoxifen: Roles of Drug Metabolizing Enzymes and Transporters, found that the enzymes used to metabolize tamoxifen in the body included: CYP2B6, CYP2C9, CYP2c19, CYP2D6 and CYP3A53. ...view middle of the document...

These standards included; postmenopausal status, having an intact uterus, at least one double endometrial thickness measurement available, prescribed tamoxifen 20 mg daily for at least 3 month at the time the ultrasound was done, and germline DNA available1. There was a total of 184 woman selected to participate in the research who were broken up into two distinct groups1. The two groups were based on measurements of their double endometrial thickness; DET of < 5mm and DET of ≥ 5mm1. Each participant’s germline DNA was then analyzed, showing individual single nucleotide polymorphisms (SNPs) 1. The 3 categories of tamoxifen metabolizers were Extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM) 1. In order to process each genotyped SNP, Hardy-Weinberg equilibrium was used1.
Discussion
The result of the study showed that the rs1800716 variant in CYP2D6 does lower endoxifen concentrations1. Patients who carry the rs1800716 mutant will have an increased chance of having a DET ≥ 5mm and a higher risk of more severe diseases, due to higher concentrations of tamoxifen, and lower concentrations of endoxifen1. This study would have presumed that a correlation existed between the homozygous mutants and woman who were poor metabolizers, but there appeared to be no correlation present1. This may have been due to not looking at every variant in the CYP450 enzymes, or missing some poor metabolizers1. There were some limitations that existed in the study that may lead to more research in the future. These limitations included; the fact that some women with a DET of < 5mm may have experienced an increase in DET if they had ultrasounds done later on in the study, there was no way to show any contrast in DET before these woman started tamoxifen, and there was no data collected on any interfering factors with tamoxifen metabolism1. Even though the...

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