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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 analyze the polymorphisms of 5-Fu metabolites such as dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) In Chongqing patients with tumor distribution characteristics for the clinical prediction of 5-Fu efficacy and adverse reactions to the genetic basis. Methods The genotypes of DPYD IVSI4 + 1 locus, TS3-’UTR locus and MTHFR C667T and A1298C in 60 patients with cancer in Chongqing area were detected by direct sequencing of PCR products. Results (1) The genotypes of DPYD IVSI4 + 1 in DPYD patients were all G / G genotypes and no G / C and C / C genotypes were found to be associated with 5-Fu toxicity. (2) TS 3- The distribution of UTR + 6 / + 6bp, + 6 / -6bp and - / - 6bp genotypes were 1.6% (1/60), 61.7% (37/60) and 36.7% (22/60) ) CTH, C / T and T / T genotypes of C667T loci in MTHFR were 33.3% (20/60) 6,1.7% (37/60) and 5% (3/60) The distribution of point A / A, A / C and C / C genotypes were 63.3% (38/60), 36.7% (22/60) and 0.1% of C / C genotype respectively. CONCLUSIONS: The genotypes of DPYD IVSI4 + 1 in Chongqing are mainly G / G genotypes, suggesting that 5-Fu is less toxic to cancer patients in this region. The polymorphisms of C667T and A1298G in TS3-’UTR and MTHFR Distribution similar to other parts of the country, the results suggest that 5-Fu in Chongqing patients with moderate effectiveness. Tumor patients with the best combination of chemotherapy to develop individualized treatment programs, so as to achieve the best therapeutic effect.