Dihydropyrimidine dehydrogenases and cytidine‐deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy

Background and Objectives Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene ( DPYD ) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5‐fluorouracil derivatives. Cytidine‐deaminase gene ( CDA ) polymorphisms have been involved in prognosis in experimental tumours. Methods Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms of genes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild‐type or at least one polymorphism) was correlated with outcome and toxicity. Results Polymorphisms frequencies wild‐type/non‐wild‐type were 36/14 in DPYD1 ( A / G ; Ile543Val ); 26/24 in DPYD2 ( C / T ; Arg29Cys ); and 17/23 in CDA ( A / C ; Lys27Gin ) or between homozygous/heterozygous were 39/11 in DPYD1 ; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow‐up (SD = 26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non‐wild‐type over wild‐type ( P  = 0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested ( P  = 0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous. Conclusions Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5‐fluorouracil‐based adjuvant chemotherapy. J. Surg. Oncol. 2008;98:130–134. © 2008 Wiley‐Liss, Inc.