Pharmacogenomic analysis to predict relapse in curatively resected gastric cancer patients treated with adjuvant 5-fluorouracil/cisplatin (FP) chemotherapy.

4057 Background: Thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are known to be key enzymes in 5-FU metabolism and play a role in resistance to fluoropyrimidines. Excision repair cross complementing 1 (ERCC1) is essential for nucleotide excision repair pathway and is thought to play key role in platinum resistance. The aim of this study was to analyze pharmacogenomic influence on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection.,Normal and cancer tissue were separately obtained from surgically resected samples with primary gastric cancer of patients with AJCC stage III-IV (M0), treated with adjuvant FP chemotherapy. TS tandem repeats, DPD exon 14 mutation, and ERCC1 8092/19007 single nucleotide polymorphism (SNP) were analyzed using extracted DNA from both tissues. TS, DPD, TP, and ERCC1 protein contents were measured by immunihistochemistry. The percentage of stained cells was multiplied by the staining intensity (0 to 3+).,Genotypes of TS, DPD, and ERCC1 were not significantly different between normal and cancer tissue. But TS, TP and ERCC1 protein were significantly over-expressed in cancer tissue. TS genotypes were as follows: 2R/2R 5.5%, 2R/3R 25.5%, and 3R/3R 69.1%. Exon 14 mutation of DPD was not observed. ERCC1 genotypes at 8092 were as follows: CC 44.2%, AC 46.8% and AA 9.1%. ERCC1 genotypes at 19007 were as follows: GG 69.3%, GA 28% and AA 5.3%. Although other protein expressions were not different from genotype to genotype, the ERCC1 protein expression was significantly lower in AA genotype of ERCC1 19007 than GA/GG genotypes. ERCC1 G19007A was significant predictor of relapse by stages (50.0% vs. 30.7% vs 0%, p<0.01). ERCC1 expression was significantly lower in relapse than in non-relapse (p=0.022).,ERCC1 G19007A polymorphism is predictor of relapse according to the stages. ERCC1 expression was significantly lower in relapse than in non-relapse, that was opposite to previous reports. Pharmacogenetic genotyping appears to predict relapse in curatively resected stage III-IV gastric cancer patients. No significant financial relationships to disclose.