Abstract: Objective　To investigate the frequency of UGT1A1＊28 and UGT1A1＊6 gene polymorphisms in cancer patients in some areas of China，and explore the distribution difference of the frequency of UGT1A1＊28 and UGT1A1＊6 gene among cancer patients.Methods　241 hospitalized cancer patients who were treated with irinotecan in Linyi People’s Hospital Affiliated to Shandong University,Linyi Cancer Hospital,the First Affiliated Hospital of Lanzhou University,the First Affiliated Hospital of Xi’an Jiaotong University and Xijing Hospital from August 2011 to April 2014,underwent UGT1A1＊28 genetic polymorphism analysis,among whom 177 patients underwent UGT1A1＊6 genetic polymorphism analysis.Genomic DNA was extracted,UGT1A1 gene was amplified by PCR,DNA sequencing was used to know the genotype distribution of UGT1A1＊28 and UGT1A1＊6 gene.Results　241 patients underwent UGT1A1＊28 genetic polymorphism analysis,TA sequences in UGT1A1＊28 gene promoter region repeated for 6 times （TA6/6） among 180 cases （74.7％）,that is,wild homozygous genotype，TA sequences repeated for 6 times or 7 times （TA6/7） among 56 cases （23.2％）,that is,heterozygous mutant genotype，and TA sequences repeated for 7 times （TA7/7） among 5 cases （2.1％）,that is,homozygous mutant genotype；177 cases underwent UGT1A1＊6 genetic polymorphism analysis，106 cases （59.9％） were wild homozygous genotype，62 cases （35.0％） were heterozygous mutant genotype，and 9 cases（5.1％）were homozygous mutant genotype.There was significant difference in the distribution of gene polymorphisms between UGT1A1＊28 and UGT1A1＊6 gene （P<0.05）.There was no significant difference in the distribution of UGT1A1＊28 genotype among groups with different gender,age,tumor location and hometown （P>0.05）.There was no significant difference in the distribution of UGT1A1＊6 genotype among groups with different gender,age and hometown （P>0.05）;there was significant difference in the distribution of UGT1A1＊6 genotype among groups with different tumor location （P<0.05）.There was significant difference in the distribution of gene polymorphisms between UGT1A1＊28 and UGT1A1＊6 gene among male group,<40 years old group,intestinal tumor group,Shandong region group and Gansu region group,respectively （P<0.05）.There was no significant difference in the distribution of gene polymorphisms between UGT1A1＊28 and UGT1A1＊6 gene among female group,40-60 years old group,>60 years old group,lung tumor group,stomach tumor group,Shaanxi region group and other region group,respectively （P>0.05）.Conclusion　The frequencies of wild homozygous genotype in UGT1A1＊28 and UGT1A1＊6 gene among cancer patients are relatively high.There was significant difference in the distribution of gene polymorphisms between UGT1A1＊28 and UGT1A1＊6 gene.In order to study UGT1A1 gene and side effects of irinotecan better,mutant sites of both UGT1A1＊28 and UGT1A1＊6 should be tested,and gender,age,tumor location,hometown of patients should be paid attention to.

Key words: Neoplasms, Genes, Mutation, UGT1A1＊28, UGT1A1＊6

摘要： 目的　调查我国部分地区肿瘤患者UGT1A1＊28和UGT1A1＊6位点基因多态性分布情况，明确二者在肿瘤患者中分布的差异。方法　收集2011年8月—2014年4月山东大学附属临沂市人民医院、临沂市肿瘤医院、兰州大学第一附属医院、西安交通大学第一附属医院、西京医院应用伊立替康治疗的住院肿瘤患者241例，均进行了UGT1A1＊28位点基因多态性检测，其中177例同时进行了UGT1A1＊6位点基因多态性检测，提取基因组DNA，PCR扩增UGT1A1基因片段，检测UGT1A1＊28和UGT1A1＊6位点基因型分布。结果　241例检测UGT1A1＊28位点基因多态性的患者中，UGT1A1＊28位点基因启动子区TA序列呈6次重复的野生型（TA6/6）即野生型纯合子180例（74.7％），TA序列6次和7次重复的杂合突变型（TA6/7）即突变型杂合子56例（23.2％），TA序列7次重复的纯合突变型（TA7/7）即突变型纯合子5例（2.1％）；177例检测UGT1A1＊6位点基因多态性的患者中，UGT1A1＊6位点基因型为野生型（G/G）即野生型纯合子106例（59.9％），杂合突变型（G/A）即突变型杂合子62例（35.0％），纯合突变型（A/A）即突变型纯合子9例（5.1％）。UGT1A1＊28和UGT1A1＊6位点基因型分布比较，差异有统计学意义（P<0.05）。不同性别、年龄、肿瘤部位、地区来源肿瘤患者UGT1A1＊28位点基因型分布比较，差异均无统计学意义（P>0.05）。不同性别、年龄、地区来源肿瘤患者UGT1A1＊6位点基因型分布比较，差异均无统计学意义（P>0.05）；不同肿瘤部位患者UGT1A1＊6位点基因型分布比较，差异有统计学意义（P<0.05）。男性、<40岁、肠道、山东地区、甘肃地区肿瘤患者UGT1A1＊28与UGT1A1＊6位点基因型分布比较，差异有统计学意义（P<0.05）；女性、40～60岁、>60岁、肺部、胃部、其他部位、陕西地区、其他地区肿瘤患者UGT1A1＊28与UGT1A1＊6位点基因型分布比较，差异无统计学意义（P>0.05）。结论　国内肿瘤患者中UGT1A1＊28和UGT1A1＊6位点基因野生型纯合子频率均较高，但两位点基因型分布有差异,所以研究UGT1A1基因与伊立替康毒副作用时应联合检测UGT1A1＊28和UGT1A1＊6两个突变位点，并且应同时注意患者的性别、年龄、肿瘤部位及地区来源。

关键词: 肿瘤, 基因, 突变, UGT1A1＊28, UGT1A1＊6