title: Correlation of UGT1A1 and ERCC1 gene polymorphisms with the outcome of combined irinotecan plus cisplatin treatment in recurrent ovarian cancer.
abstract: The aim of this study was to define the genotypes of UGT1A1 and ERCC1 and to examine their relationship with the efficacy and toxicity of a combination therapy of irinotecan and cisplatin in patients with advanced ovarian cancer. The allelic frequencies of the UGT1A1 and ERCC1 variants in a group of 89 patients with advanced ovarian cancer were determined. The relationship between the adverse events of irinotecan-based chemotherapy and the efficacy of cisplatin in patients with advanced ovarian cancer were analyzed. For patients who carried the UGT1A1*28 wild-type (WW) or the UGT1A1*28 heterozygous and homozygous mutant (WM+MM) genotypes, the incidences of grade 2 or 3 tardive diarrhea were 52.2 and 72.7% respectively, and the difference was statistically significant (P = 0.031, OR = 2.1, 95%CI = 1.6-9.2). For grade 3 or 4 tardive diarrhea, the incidence rates were 7.5 and 36.4% respectively; this difference was also statistically significant (P = 0.000, OR = 4.9, 95%CI = 3.3-15.8). The response rates of ERCC1 WW and ERCC1 WM+MM carriers were 30.3 and 20.2% respectively; this difference was significant (P = 0.032, OR = 3.2, 95%CI = 1.4-9.1). Together, the results from this study suggest that UGT1A1 is a target gene for tardive diarrhea, and that the UGT1A1*28 gene mutation might increase the risk of diarrhea with irinotecan-based chemotherapy. Furthermore, the results suggest that ERCC1 WW carriers might obtain a better rate of clinical response from a combined irinotecan and cisplatin regimen than ERCC1 WM+MM carriers.
authors.affiliation: General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: General Hospital of Beijing Military Region, Beijing, China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ding
authors.affiliation: General Hospital of Beijing Military Region, Beijing, China.
authors.forename: L X
authors.initials: LX
authors.lastname: Song
authors.affiliation: General Hospital of Beijing Military Region, Beijing, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D003967:Diarrhea / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D002945:Cisplatin; D004268:DNA-Binding Proteins; D004720:Endonucleases; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme; C071447:ERCC1 protein, human