Polymorphism in the 3'-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy.
To investigate the relationship between polymorphism in the 3'-untranslated region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA from peripheral blood leukocytes was obtained before therapy. TS 3'-UTR genotypes were detected by PCR-RFLP. Polymorphism in the TS 3'-UTR can be classified into three groups according to the presence or absence of a 6 bp nucleotide fragment: the -6/-6 bp, -6/+6 bp and +6/+6 bp groups. The response rate of the -6/-6 bp and -6/+6 bp groups was found to be significantly higher than the +6/+6 bp group. These results show that the presence of the TS 3'-UTR 6 bp nucleotide fragment can be correlated with the sensitivity of gastric cancer to 5-FU-based chemotherapy, and that the TS 3'-UTR polymorphism profile can be used to guide the choice of 5-FU-based chemotherapy in advanced gastric cancer.
Lu
Jian-Wei
JW
Department of Medical Oncology, Jiangsu Province Institute of Cancer Research, Nanjing, 210009, PR China.
Gao
Chang-Ming
CM
Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, 210009, PR China.
Wu
Jian-Zhong
JZ
Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, 210009, PR China.
Cao
Hai-Xia
HX
Department of Epidemiology, Jiangsu Province Institute of Cancer Research, Nanjing, 210009, PR China.
Tajima
Kazuo
K
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan.
Feng
Ji-Feng
JF
Department of Medical Oncology, Jiangsu Province Institute of Cancer Research, Nanjing, 210009, PR China. lujw5@yahoo.com.
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D017931:DNA Primers; D013940:Thymidylate Synthase; D005472:Fluorouracil