重庆地区5-氟尿嘧啶代谢相关酶的基因多态性分布

Gene polymorphism of 5-Fluoropyrimidine-related enzymes in cancer patients*

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.