伊立替康所致不良反应与UGT1A1~*28基因多态性的临床研究

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目的检测恶性肿瘤患者UGT1A1*28基因多态性的分布情况,探讨其与伊立替康所致不良反应的关系。方法对63例恶性肿瘤外周血标本采用PCR扩增和基因测序的方法检测UGT1A1*28的基因型TA(6)/TA(6)纯合子、TA(6)/TA(7)杂合子、TA(7)/TA(7)纯合子。结果迟发性腹泻的发生上一般临床特征如患者的年龄、性别、ECOG评分、复发转移灶、合并疾病史、剂量强度差异均无统计学意义(P>0.05);而在中性粒细胞减少的发生上,剂量强度是危险因素(P<0.05),余各项特征差异无统计学意义(P>0.05);TA(6)/TA(6)正常野生型48例(76.19%),TA(6)/TA(7)杂合基因型15例(23.81%),TA(7)/TA(7)纯合突变型0例;基因TA(6)/TA(6)野生型与TA(6)/TA(7)杂合型在患者的性别、年龄、ECOG评分、合并疾病、原发灶的部位与复发转移灶临床特征之间差异均无统计学意义(P>0.05)。结论 UGT1A1*28基因TA(6)/TA(6)野生型最为常见,TA(6)/TA(7)杂合型次之;迟发性腹泻的发生与剂量强度无明显相关性,UGT1A1*28基因多态性是腹泻危险因素,TA(6)/TA(7)型基因患者迟发性腹泻的发生率增加;中性粒细胞减少的发生与剂量强度呈正相关,剂量强度越大的患者可能越易发生中性粒细胞的减少。 Objective To detect the distribution of UGT1A1 * 28 gene polymorphism in patients with malignant tumors and to explore its relationship with irinotecan-induced adverse reactions. Methods The genotypes of TA (6) / TA (6) homozygotes and TA (6) / TA (7) heterozygotes of UGT1A1 * 28 were detected by PCR and sequencing in 63 cases of malignant tumor. (7) / TA (7) homozygotes. Results There was no significant difference in the general clinical features such as age, sex, ECOG score, recurrence and metastasis, history of combined disease and dose intensity among patients with delayed diarrhea (P> 0.05). However, in neutropenia (P <0.05). There was no significant difference in all the features between the two groups (P> 0.05). TA (6) / TA (6) (6) / TA (7) heterozygous genotype in 15 cases (23.81%), TA (7) / TA (7) homozygous mutation in 0 cases; gene TA (6) / TA 6) / TA (7) There was no significant difference in heterozygous type between the gender, age, ECOG score, combined disease, clinical features of primary tumor and recurrence and metastasis (P> 0.05). CONCLUSION: The wild type of TA (6) / TA (6) is most common in UGT1A1 * 28 gene and the heterozygote of TA (6) / TA (7) is the second most common type. There is no significant correlation between the occurrence of delayed diarrhea and dose intensity. UGT1A1 * 28 gene polymorphism is a risk factor for diarrhea. The incidence of delayed diarrhea is increased in patients with TA (6) / TA (7) gene. The incidence of neutropenia is positively correlated with the dose intensity, the greater the dose intensity May be more prone to neutrophil reduction.
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