Grau Juan J, Caballero Miguel, Monzó Mariano, Muñoz-García Carmen, Domingo-Domenech Jose, Navarro Alfons, Conill Carlos, Campayo Marc, Bombí Jose A
Oncology Department, Institut Clinic de Malalties Hemato-Oncològiques (ICMHO) of Hospital Clínic, IDIBAPS (Augusto Pi i Sunyer Memorial Institute for Biomedical Research), and University of Barcelona, Barcelona, Spain.
J Surg Oncol. 2008 Aug 1;98(2):130-4. doi: 10.1002/jso.21096.
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.
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.
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.
Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.
二氢嘧啶脱氢酶基因（DPYD）的单核苷酸多态性会导致二氢嘧啶脱氢酶（DPD）缺乏，从而使5-氟尿嘧啶衍生物的活性增加。胞苷脱氨酶基因（CDA）多态性与实验性肿瘤的预后有关。
分析50例连续接受替加氟辅助化疗的胃癌切除患者的DPYD1基因（A/G；Ile543Val）、DPYD2基因（C/T；Arg29Cys）和CDA基因（A/C；Lys27Gln）的多态性。等位基因状态（野生型或至少一种多态性）与预后和毒性相关。
DPYD1基因（A/G；Ile543Val）野生型/非野生型的多态性频率为36/14；DPYD2基因（C/T；Arg29Cys）为26/24；CDA基因（A/C；Lys27Gln）为17/23；或者纯合子/杂合子之间DPYD1基因分别为39/11，DPYD2基因分别为33/17，CDA基因分别为26/24。中位随访77个月（标准差=26.3）后，18例患者死于肿瘤复发。仅在DPYD1基因患者中观察到，非野生型患者比野生型患者有更好的生存率（P=0.0214）；并且在检测的三个基因中任何一个有一个或多个杂合多态性的患者中也有更好的生存率（P=0.0017）。10例患者（20%）因毒性而减少了总剂量，其中只有3例是纯合子。
DPYD和CDA基因多态性可预测接受基于5-氟尿嘧啶辅助化疗的胃癌患者的生存率。
