Correlation Study between CYP2C8 Gene Polymorphim and Adverse Reaction of Paclitaxel in Cancer Patients / 中国药学杂志

OBJECTIVE: To investigate the correlation between CYP2C8 gene polymorphisms and the adverse reactions of paclitaxelin in cancer patients.METHODS: Fifty-two patients who received paclitaxel chemotherapy from January 2016 to May 2018 were selected as experimental subjects. The CYP2C8 genotypes of the selected patients were tested and the adverse reactions of paclitaxel were observed, collected and recorded to explore the relationship between adverse reactions and genetic polymorphism.RESULTS: In this study, 25 gene loci were detected, only 7 gene loci had mutation, and the remaining 18 gene loci were all wild-type.In the polymorphism of CYP2C8 gene,the incidence of thrombocytopenia and pain in patients with CYP2C8*1B(-271C>A) wild-type (CC) was significantly higher than that in mutant (CA+AA) (PT) wild-type gene (CC) was significantly lower than that in mutant gene (CT+TT) (P<0.05).CONCLUSION: The polymorphism of CYP2C8 gene may be associated with the adverse reaction of paclitaxel.

Genetic Polymorphisms of CYP2C8 in A Healthy Iranian Population.

Aim: The aims of this study were to genotype CYP2C8 in an Iranian population and compare their allelic frequencies with other ethnic groups. Study Site and Duration: Biotechnology Department, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran from June 2012 through May 2013. Methodology: CYP2C8 (*1/*2/*3) allelic variants were determined in 200 unrelated healthy Iranian volunteers by real time-polymerase chain reaction (PCR). Results: A total 156 subjects (78%) were homozygous for CYP2C8*1, six subjects (3%) were homozygous for CYP2C8*2 and 38 subjects (19%) were heterozygous CYP2C8*1/*2. CYP2C8*3 was not detected. Discussion and Conclusion: Genotyping indicated no significant (P>0.05) difference between CYP2C8 allelic variant frequencies in an Iranian compared with Burkina Faso population. The Iranian population’s CYP2C8 allelic variation was significantly (P<0.05) different when compared with populations in Portugal, African-American race to Malaysia, Ghana, Zanzibar, Spain, Czech Republic and Sweden.

Frequencies of Cytochrome P450 2B6 and 2C8 Allelic Variants in the Mozambican Population

Background: The cytochrome P450 enzymes (CYP) play an important role in the metabolism of many therapeutic agents. The activities of different enzymes exhibit variability in different populations, which causes variations in drug response or toxicity. The CYP2B6 and CYP2C8 enzymes are encoded by polymorphic genes characterised by different single nucleotide polymorphisms (SNPs). Several of these CYP variants are often associated with slow metabolism phenotypes. This study aimed to analyse the frequencies of allelic variants of CYP2B6 and CYP2C8 in the Mozambican population. Methods: Using a polymerase chain reaction and restriction fragment length polymorphism assay (PCR-RFLP), the frequencies of the allelic variants of CYP2B6 (c.64C>T, c.516G>T, c.777C>A, c.785A>G, c.1459C>T) and CYP2C8 (c.805A>T, c.416G>A, c.1196A>G, c.792C>G) were determined in 360 Mozambican blood donors. Results: The frequencies of the allelic variants of the CYP2B6 gene were 0.057, 0.426, 0.0, 0.410, and 0.004. For the CYP2C8 gene, the frequencies of the allelic variants were 0.160, 0.048, 0.0, and 0.005. No significant differences were observed between the gender and geographic distribution of volunteers around the country. Conclusion: The frequencies of the allelic variants of the CYP2B6 and CYP2C8 genes were found to be homogeneously distributed in the Mozambican population and were comparable to other African populations. Further studies are required to explore the impact of these variants on the clinical response (efficacy and toxicity) of drugs, including antimalarials.

Identification of CYP2C8 gene polymorphisms in Korean patients with epithelial ovarian cancer and their association with effect and toxicity of anticancer drug / 대한산부인과학회지

OBJECTIVE: The frequency of CYP2C8 gene polymorphisms in Korean patients with epithelial ovarian cancer was identified and their association with toxicity and effect of the anticancer drug according to haplotypes was analyzed. METHODS: DNA was extracted from 57 epithelial ovarian cancer patients between January 2004 and March 2005. Genetic variations that are three common SNPs (CYP2C8*1D; -411T>C, CYP2C8*1C; -370T>G and CYP2C8*1B; -271C>A) by direct sequence analysis from 57 Korean women with epithelial ovarian cancer were observed. 33 patients who received debulking surgery, were diagnosed over FIGO state III, serous ovarian cancer were enrolled and received paclitaxel based chemotherapy. Among 33 patients 21 chemo-sensitive patients and 12 resistant patients were analyzed. Using these SNPs, We constructed haplotypes and haplotype pairs. CYP2C8 genotypes according to the clinical characteristics were analyzed and evaluated. RESULTS: Genetic analysis revealed the common SNPs' allele frequencies of -411T>C, -370T>G, and -271C>A were 0.3, 0.44, and 0.1. Two common SNPs allele frequency was similar to the data in Korean population substantially, but CYP2C8*1C frequency was more frequent in epithelial ovarian cancer patients and especially in FIGO stage III. Disease free interval in CYP2C8*1C homologous group was longer than others. CONCLUSION: CYP2C8*1C SNPs were detected more frequently in epithelial ovarian cancer patients and especially in FIGO stage III patients. CYP2C8*1C homologous patients had more longer disease free interval than others.