Identification of CYP2C8 gene polymorphisms in Korean patients with epithelial ovarian cancer and their association with effect and toxicity of anticancer drug.
- Author:
Sung Ook HWANG
1
;
Eun Seop SONG
;
Woo Young LEE
;
Yong Il JI
;
Yong Man KIM
;
Young Tak KIM
;
Jung Eun MOK
Author Information
1. Department of Obstetrics and Gynecology, Inha University College of Medicine, Incheon, Korea.
- Publication Type:Original Article
- Keywords:
Cytochrome P450;
CYP2C8;
SNP;
Paclitaxel;
Epithelial ovarian cancer
- MeSH:
Cytochrome P-450 Enzyme System;
DNA;
Drug Therapy;
Female;
Gene Frequency;
Genetic Variation;
Genotype;
Haplotypes;
Humans;
Ovarian Neoplasms*;
Paclitaxel;
Polymorphism, Single Nucleotide;
Sequence Analysis
- From:Korean Journal of Obstetrics and Gynecology
2006;49(3):553-565
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
