二氢嘧啶脱氢酶基因单核苷酸多态性与结直肠癌患者5-FU化疗毒副作用的关系

J4 ›› 2011, Vol. 37 ›› Issue (4): 707-711.

二氢嘧啶脱氢酶基因单核苷酸多态性与结直肠癌患者5-FU化疗毒副作用的关系

张锌|孙步彤|卢振霞

吉林大学中日联谊医院血液肿瘤科|吉林长春 130033

收稿日期:2011-03-18 出版日期:2011-07-28 发布日期:2011-07-28
通讯作者: 卢振霞（Tel：0431-84995812，E-mail：lzx2010@yahoo.com.cn) E-mail:lzx2010@yahoo.com.cn
作者简介:张锌（1981-）|男|吉林省公主岭市人|医学硕士|主要从事血液病及恶性肿瘤分子生物学发病机制与临床研究。
基金资助:
吉林省科技厅科技发展计划项目资助课题（20050405-4）

Relationship between SNP of DPYD and 5-fluorouracil toxicity in colorectal cancer patients

ZHANG Xin |SUN Bu-tong |LU Zhen-xia

Department of Hematology and Oncology,China-Japan Union Hospital|Jilin University|Changchun |130033|China

Received:2011-03-18 Online:2011-07-28 Published:2011-07-28

摘要/Abstract

摘要：

目的：探讨二氢嘧啶脱氢酶基因(DPYD)单核苷酸多态性(SNP)与5-氟尿嘧啶（5-FU）化疗毒性反应的相关性，为结直肠癌的个体化治疗提供依据。方法：对60份结直肠癌患者的EDTA抗凝外周血提取基因组DNA后进行实时定量PCR，测定DPYD的14G1A、G2194A、T85C、G1156T和T464A等位点的SNP，并统计上述60例患者化疗后发生的毒副作用，分析DPYD的SNP与5-FU化疗毒副作用的相关性。结果：① 60例标本中未检测到14G1A、G1156T多态性位点变异； G2194A杂合型6例(10.0％)，野生型54例(90.0％)；T464A杂合型2例(3.3％)，野生型58例(96.7％)； T85C突变型2例(3.3％)，杂合型8例(13.3％)，野生型50例(83.4％)； ②T85C多态性位点无SNP突变者消化道毒性发生率为14％(7／50 )，血液学毒性发生率为4％(2／50)；存在SNP突变者消化道毒性发生率为60％(6／10)，血液学毒性发生率为70％(7／10)，差异有统计学意义(P<0.05)。 T464A有 SNP突变者胃肠道反应和骨髓抑制发生率为50%（1／2）和100％(2／2)，高于无SNP突变者的21%(12／58) 和12%(7／58)，差异有统计学意义(P<0.05)。③ G2194A有SNP突变者胃肠道反应和骨髓抑制发生率为33%（2／6）和50％(3／6)，高于无SNP突变者的20%(11／54) 和11%(6／54)，差异有统计学意义(P<0.05)。结论：DPYD的SNP与5-FU化疗的毒副反应有关，检测DPYD的SNP对预测5-FU化疗的毒副反应有一定的指导意义。

关键词: 结直肠肿瘤；二氢嘧啶脱氢酶；5-氟尿嘧啶；单核苷酸多态性

Abstract:

Objective To study the relevance between single-nucleotide polymorphism（SNP）of dihydrogenpyrimidine dehydrogenase gene （DYPD） and 5-fluorouracil（5-FU） toxicity in colorectal cancer patients and provide the evidence for individualized treatment in colorectal cancer patients.Methods The genomic DNA was extracted from EDTA anticoagulation peripheral blood in a total of 60 patients with colorectal cancer and then real-time quantitative polymerase chain reaction (PCR) was performed.The SNPs of 14G1A,G2194A,T85C,G1156T and T464A sites of DPYD were detected,the side effects of chemotherapy with 5-FU in 60 patients were recorded,the relevance between the SNP of DPYD and side effects of 5-FU chemotherapy was analyzed. Results ①14G1A and G1156T polymorphism loci transformation were not found in 60 patients. G2194A heterozygous type was found in 6 cases (10%),wild type in 54 cases (90.0%);T464A heterozygous type in 2 cases (3.3%),wild type in 58 cases (96.7%);T85C mutations type in 2 cases (3.3%),heterozygous type in 8 cases (13.3%),wild type in 50 patients(83.4%).②The incidence of gastrointestinal tract toxicity in patients with T85C polymorphism sites without SNP mutation was 14% (7/50),the incidence of hematological toxicity was 4% (2/50);the incidence of gastrointestinal tract toxicity in patients with T85C polymorphism sites with SNP mutation was 60% (6/10),the incidence of hematological toxicity was 70% (7/10),the differences were statistically significant (P<0.05);the incidences of gastrointestinal reaction andbone marrow restrain in patients with T464A SNP mutation were 50% (1/2) and 100% (2/2),in patients without SNP mutation were 21% (12/58) and 12% (7/58),the differences were statistically significant (P<0.05). ③ The incidences of hematological toxicity and bone marrow restrain in patients with G2194A SNP mutation were33% (2/6) and 50% (3/6), in the patients without SNP mutation were 20% (11/54) and 11 (6/54),the differences were statistically significant (P<0.05). Conclusion The SNP of DPYD has correlation with the adverse reactions of 5-FU chemotherapy.The detection of SNP of DPYD may predict the serious adverse reactions of 5-FU chemotherapy.

Key words: colorectal neoplasms；dihydrogenpyrimidine dehydrogenase gene；5-fluorouracil；single nucleotide polymorphism

中图分类号:

R735.3

张锌|孙步彤|卢振霞. 二氢嘧啶脱氢酶基因单核苷酸多态性与结直肠癌患者5-FU化疗毒副作用的关系[J]. J4, 2011, 37(4): 707-711.

ZHANG Xin |SUN Bu-tong |LU Zhen-xia. Relationship between SNP of DPYD and 5-fluorouracil toxicity in colorectal cancer patients[J]. J4, 2011, 37(4): 707-711.