Relationship between SNP of DPYD and 5-fluorouracil toxicity in colorectal cancer patients
Relationship between SNP of DPYD and 5-fluorouracil toxicity in colorectal cancer patients
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发表时间：
2011
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通讯作者：
Lu Zhen-xia
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作者：
Lu Zhen-xia
目的 研究结直肠癌患者二氢嘧啶脱氢酶基因（DYPD）单核苷酸多态性（SNP）与5-氟尿嘧啶（5-FU）毒性的相关性，为结直肠癌患者个体化治疗提供依据。方法 提取60例结直肠癌患者经EDTA抗凝的外周血基因组DNA。 检测DPYD的14G1A、G2194A、T85C、G1156T和T464A位点的SNP，记录60例患者接受5-FU化疗的副作用，分析DPYD的SNP与5-FU化疗副作用的相关性。 ①60例患者均未发现14G1A、G1156T多态性位点转化。其中G2194A杂合型6例（10%），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 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突变的患者胃肠道毒性发生率为14%（7/50），血液学毒性发生率为4%（2/50）；无SNP突变的患者胃肠道毒性发生率为4%（2/50）。 T85C多态性位点有SNP突变者占60%(6/10),血液学毒性发生率为70%(7/10),差异有统计学意义(P0.05);T464A SNP突变者胃肠道反应和骨髓抑制发生率分别为50%(1/2)和100%(2/2),无SNP突变者为100%(2/2)。 21%(12/58)和12%(7/58),差异有统计学意义(P<0。05)。③G2194A SNP突变患者血液学毒性和骨髓抑制发生率分别为33%(2/6)和50%(3/6),无SNP突变患者分别为20%(11/54)和11(6/54),差异有统计学意义 显着性(P<0。05)。结论DPYD的SNP与5-FU化疗的不良反应具有相关性。DPYD的SNP检测可以预测5-FU化疗的严重不良反应。
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(P0.05);the incidences of gastrointestinal reaction and bone 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(P0.05).③ The incidences of hematological toxicity and bone marrow restrain in patients with G2194A SNP mutation were 33%(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(P0.05).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.