Pharmacogenomics of colorectal cancer in the Taiwanese population

• Main Authors: Chi-Fang Chen, 陳吉芳
• Other Authors: Chung-Yung Chen
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/54969422648276396465

碩士 === 中原大學 === 化學研究所 === 95 === The polymorphisms in the human genomics are various in different populations. Some of these variations can lead to differential levels in gene expression and in enzyme activity and thus can affect the metabolic pathway of 5-Fluorouracil (5-FU) and related drugs. This also happens to other drugs against colorectal cancer (CRC), including capecitabine, irinotecan and oxaliplatin, etc. 5-FU and Oxaliplatin have been approbated for anti-cancer therapy by the department of Health in Taiwan. The target gene of 5-FU is Thymidylate Synthase (TS), high activity of TS result in low efficiency of the 5-FU chemotherapy. We use the PCR and Sequencing technology to analyse SNP. Also , we screen SNPs in all of the TS, DPYD, ERCC1 and TP’s exon regions from 40 Taiwan volunteers. The results of SNP screening have been discovered as 381A>G (allele frequency : 7/60 = 11.67%) in TS gene exon 3； 496A>G (allele frequency : 3/78=3.85%), 1627A>G (allele frequency : 3/78=3.85%) and 1896C>T (allele frequency : 10/14=71.43%) in DPYD exon 6, 13 and 14 respectively. The recent report indicated those three types of DPYD polymorphisms will induce severe cytotoxic in patients who treated 5-FU. ERCC1 codon 118 C→T (354C>T, allele frequency : 19/34=55.88%) polymorphism showed that 88.24% were heterozygous (C/T genotype), 11.76% were homozygous for AAT codon, and 0% were homozygous for codon AAC. In this research of CRC SNP screening, we are the first performance to whole exons screening in TS, DPYD, ERCC1 and TP respectively. The aims of this study are to improve the effect of the chemotherapy in CRC and reduce the toxicity of chemotherapy.