Korean J Obstet Gynecol.  2006 Mar;49(3):553-565.

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

• Hwang SO
• Song ES
• Lee WY
• Ji YI
• Kim YM
• Kim YT
• Mok JE

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.

Keyword

Cytochrome P450; CYP2C8; SNP; Paclitaxel; Epithelial ovarian cancer

MeSH Terms

Cytochrome P-450 Enzyme System
DNA
Drug Therapy
Female
Gene Frequency
Genetic Variation
Genotype
Haplotypes
Humans
Ovarian Neoplasms*
Paclitaxel
Polymorphism, Single Nucleotide
Sequence Analysis
Cytochrome P-450 Enzyme System
DNA
Paclitaxel