文档介绍：进行病例对照研究,应用 PCR-RFLP 方法检测其 CYP2E1 基因型及等位
基因频率并进行比较。结果:CYP2E1 基因型分布与乳腺癌易感性有关(P<),c2/c2 基因型携带者换乳腺癌危险度是其他基因型携带着的 倍(95% confidence interval = ~; P = )。结论:CYP2E1 基因多态性与乳腺癌易感性有关,与性别无关。
关键词 CYP3A5,CYP2D6,CYP2E1,他莫昔芬,乳腺癌,相关性
INFLUENCE OF IC POLYMORPHISM ON TAMOXIFEN PLASMA CONCENTRATION AND SUSCEPTIBILITY OF BREAST CANCER PATIENTS
ABSTRACT
Tamoxifen (TAM),a steroidal anti-estrogen drug, is widely used in the prevention and treatment of estrogen receptor (ER)-positive breast cancer. Because of tamoxifen’s individual bioavailability differences and its significant side effects to the patients, these brought a lot of difficulties to the individualized medicine. In particular, the differences in plasma concentration of different individuals who take the same oral dose of tamoxifen are very large. It suggests differences in ic background may be one of the factors of the differences in plasma concentration.
In this study, polymerase chain reaction (PCR) was used to genotye human cytochrome P450 enzymes CYP3A5*3, CYP2D6*10, and high-performance liquid chromatography - mass spectrometry (LC-MS/MS)
was used to determine blood concentration of tamoxifen and its active metabolite 4 - hydroxy tamoxifen (HTAM) in patients with breast cancer. Then we used statistical methods to analyze relationship between gene polymorphism and tamoxifen plasma concentration, which could provide a theoretical basis for individualized medicine. And we wanted to explore the correlation between the genotype of CYP2E1 and the susceptibility of breast cancer.
Part One: Study of determinations of CYP3A5*3, CYP2D6*10’s genotypes
Objective: To establish a genotyping method of CYP3A5*3 and CYP2D6*10 genotype of the breast cancer patients. Methods: In 30 cases of breast cancer
patients,phenol - chloroform method was used to extract genomic DNA from
the blood specimens, and PCR-RFLP method was used to test the genomic DNA samples, and a gel electrophoresis genotyping experiments was