title: UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer.
abstract: To investigate the relationship between uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1)*28/*6 and toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer (CRC) in Xinjiang Uygur and Han population.
  
  
  
  A total of 183 patients (Uygur, 114; Han, 69) with advanced CRC who received the irinotecan-based chemotherapy were enrolled in this retrospective analysis. Polymerase chain reaction amplification and direct sequencing method were used for UGT1A1*28 and UGT1A1*6 polymorphism detection. The patients were followed up to analyze the relationship between different genotypes with adverse reactions and the clinical outcome of irinotecan-based chemotherapy.
  
  
  
  Significant differences were found in genotype frequencies of UGT1A1*28 and UGT1A1*28/*6 between Uygur and Han (P = 0.02 and P = 0.002). Uygur and Han patients carrying wild UGT1A1*28 and *6 genotypes appeared to have significantly lower diarrhea incidence (I/II and III/IV) than those carrying mutant genotypes (all P < 0.05). In Uygur patients, UGT1A1*28 genotypes were related with objective response rate and disease control rate (P < 0.05). Compared with *1 allele *1/*1, *1 allele *1/*28*1/*28 mutant of UGT1A1*28 was associated with shorter OS in both Uygur and Han ethnicities (all P < 0.05). Compared with double allele variants (DW), single allele variants (SV), and double allele variants (DV) of UGT1A1*28/*6 were associated with shorter overall survival (OS) in Uygur and Han (all P < 0.05). Cox regression analysis revealed factors significantly influencing OS, including UGT1A1*28, UGT1A1*6, combined genotypes and chemotherapy line in Ugyur, and only combined genotypes in Han (all P < 0.05).
  
  
  
  UGT1A1 gene polymorphism predicts irinotecan-related adverse reactions in advanced CRC patients of Xinjiang Uygur and Han nationality; UGT1A1 gene polymorphism is correlated with efficacy and prognosis in Uygur nationality, but only related to prognosis in Han nationality in irinotecan-based chemotherapy.
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Xushan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Saifuding
authors.initials: S
authors.lastname: Keyoumu
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 789, Suzhou East Road, Ürümqi, 830000, Xinjiang, People's Republic of China. ae717ty@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme
keywords: Advanced colorectal cancer; Clinical efficacy; Han nationality; Irinotecan-based chemotherapy; Polymorphism; Toxicity; UGT1A1; Uygur nationality