摘要
目的分析5-氟尿嘧啶(5-Fu)代谢相关酶二氢嘧啶脱氢酶(DPYD)、胸苷酸合成酶(TS)和亚甲基四氢叶酸还原酶(MTHFR)的基因多态性位点在重庆地区肿瘤患者中的分布特点,为临床提供预测5-Fu疗效及不良反应的遗传学依据。方法采用PCR产物直接测序法分别检测重庆地区60例肿瘤患者DPYD IVSI4+l位点、TS3-′UTR位点以及MTHFR C667T和A1298C的基因型。结果(1)60例肿瘤患者中DPYD IVSI4+l位点均为G/G基因型,未检测出可引起5-Fu相关毒性的G/C和C/C基因型;(2)TS 3-′UTR+6/+6bp、+6/-6bp、-/-6bp基因型分布概率分别是1.6%(1/60)、61.7%(37/60)和36.7%(22/60);(3)MTHFR的C667T位点C/C、C/T、T/T基因型分布概率分别是33.3%(20/60)6、1.7%(37/60)和5%(3/60);A1298G位点A/A、A/C、C/C基因型分布概率分别是63.3%(38/60)、36.7%(22/60),C/C基因型0.1%。结论重庆地区肿瘤患者DPYD IVSI4+l位点以G/G基因型为主,提示5-Fu对该地区肿瘤患者的毒性较弱;TS3-′UTR、MTHFR的C667T和A1298G位点基因多态性分布与国内其他地区相似,结果提示5-Fu对重庆地区患者有效性中等。肿瘤患者最好采用联合化疗制定个体化治疗方案,从而达到最佳治疗效果。
Objective To investigate the gene polymorphism of dihydropyrimidine dehydrogenase (DPYD) ,thyrnidylate synthase (TS),and methylene tetrahydrofolate reductase (MTHFR) in Chongqing cancer patients, to provide the genetic information for 5- Fu treatment. Methods DPYD IVSI4+1,TS 3'-UTR(untranslated region),MTHFR C667T and A1298C genotypes were detected by polymerase chain reaction(PCR)and gene sequencing in 60 Cbongqing cancer patients. Results (1)Of all 60 patients, there was only one DPYD IVSI4+1 G/G;(2)The proportion of TS 3'-UTR +/+6bp,+/-bp and -/-6bp genotype were 1.6%(1/60), 61.7%(37/60) and 36.7%(22/60) respectively; (3) The proportion of MTHFR 667 C/C,C/T and T/T were 33.3%(20/60),61. 7%(37/60) and 5% (3/60),While MTHFR 1298 A/A,A/C genotype were 63.3% (38/60) and 36.7%,and only one was MTHFR 1298 C/C. Conclusion In Chongqing cancer patients DPYD IVSI4+1 gene type is G/G,it could not be a prognostic factor for severe toxicity in 5-Fu based chemotherapy. The gengtic polymorphism distribution of TS 3'-UTR, MTHFRC667T and A1298C from Chongqing is close to other area in China. The cancer patients have medium sensitivity of 5-Fu in Chongqing and treated by united chemotherapy.
出处
《重庆医学》
CAS
CSCD
北大核心
2009年第14期1705-1707,1709,共4页
Chongqing medicine
基金
第三军医大学校临床科研课题基金资助。
关键词
基因多态性
5-氟尿嘧啶(5-Fu)
DPYD
TS
MTHFR
5-Fluoropyrimidine
dihydropyrimidine dehydrogenase
thymidylate synthase
methylene tetrahydrofolate reductase
polymorphism