186例消化系统恶性肿瘤患者UGT1A1*6、UGT1A1*28基因多态性的检测和分析

目的：检测和分析消化系统恶性肿瘤患者UGT1A1^*6、UGT1A1^*28基因多态性。方法：收集186例消化系统恶性肿瘤患者血液标本，采用焦磷酸测序方法对UGT1A1^*6、UGT1A1^*28基因多态性进行检测，并对基因多态性频率进行统计分析。结果：186例消化系统恶性肿瘤患者样本具有群体代表性。UGT1A1^*6基因多态性为野生型G/G占比63.4%、杂合型G/A占比32.8%、突变纯合型AA占比3.8%；UGT1A1^*28基因多态性为野生型TA6/TA6占比75.8%、杂合型TA6/TA7占比21.5%、突变纯合型TA7/TA7占比2.7%；UGT1A1^*6和^*28基因多态性为野生型G/G且TA6/TA6占比48.9%，单点变异型G/G且TA6/TA7占比12.4%、G/A且TA6/TA6占比23.1%，双点变异型G/G且TA7/TA7占比2.2%、G/A且TA6/TA7占比9.1%、A/A且TA6/TA6占比3.8%，三点变异型G/A且TA7/TA7占比0.5%。患者UGT1A1^*6与UGT1A1^*28基因多态性频率分布之间具有显著性差异（P<0.05）。3个不同年龄段患者之间，胃癌、结直肠癌、其他消化系统恶性肿瘤患者之间的UGT1A1^*28、UGT1A1^*6和^*28基因型分布具有显著性差异（P<0.05）。结论：消化系统恶性肿瘤患者应用伊立替康时，应联合检测UGT1A1^*6和UGT1A1^*28基因多态性，同时密切关注患者的肿瘤类型以及年龄差异。

Detection and analysis on gene polymorphisms of UGT1A1*6 and UGT1A1*28 in 186 patients with digestive system malignant tumors

OBJECTIVE To detect and analyze the gene polymorphisms of UGT1A1^*6 and UGT1A1^*28 in patients with digestive system malignant tumors.METHODS Blood samples from 186 patients with digestive system malignant tumors were collected.The gene polymorphisms of UGT1A1^*6 and UGT1A1^*28 were detected by pyrophosphate sequencing,and the frequencies of gene polymorphisms were analyzed statistically.RESULTS The samples from 186 patients with digestive system malignant tumors were representative of the population.In 186 patients with digestive system malignant tumors,the frequencies of UGT1A1^*6 gene polymorphism carrying G/G,G/A and A/A genotype were 63.4%,32.8% and 3.8%,respectively.The frequencies of UGT1A1^*28 gene polymorphism carrying TA6/TA6,TA6/TA7 and TA7/TA7 genotype were 75.8%,21.5% and 2.7%,respectively.The frequencies of UGT1A1^*6 and ^*28 gene polymorphism carrying G/G TA6/TA6,G/G TA6/TA7,G/A TA6/TA6,G/G TA7/TA7,G/A TA6/TA7,A/A TA6/TA6 and G/A TA7/TA7 genotype were 48.9%,12.4%,23.1%,2.2%,9.1%,3.8% and 0.5%,respectively.The distributions of genotype between UGT1A1^*6 and UGT1A1^*28 in patients with malignant tumors was significantly different (P<0.05).The distribution of UGT1A1^*28 genotype among patients in three different levels of age was significantly different,as well as the distribution of UGT1A1^*6 and ^*28 genotype (P<0.05).The distributions of UGT1A1^*28 genotype among patients with gastric cancer,colorectal cancer and other digestive system malignant tumors were significantly different,as well as the distributions of UGT1A1^*6 and ^*28 genotype (P<0.05).CONCLUSION Combined detection of UGT1A1^*6 and UGT1A1^*28 would help identification and subsequent evaluation of irinotecan therapy in patients with digestive system malignant tumors,and attention should be paid to the tumor types and age levels.