title: DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian cancer.
abstract: Epithelial ovarian cancer has a poor prognosis owing to late diagnosis and frequent relapse after first-line therapy. Analysis of individual genetic variability could aid in the identification of markers, which could help in stratifying patients with the aim of optimizing individual therapy. In this study we assessed polymorphisms in three genes important in drugs' response in 97 early and 235 late-stage ovarian cancer patients. The Asp1104His polymorphism in xpg, a gene important for removal of platinum adducts, was associated with progression-free survival in early- and late-stage ovarian cancer. Our data indicate that a simple diagnostic analysis such as xpg genotyping can help in predicting response, and extension to other possibly relevant genotypes could be useful in selecting patients with epithelial ovarian cancer for optimal therapy and hence increase the chance of response.
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Caiola
authors.forename: L
authors.initials: L
authors.lastname: Porcu
authors.forename: R
authors.initials: R
authors.lastname: Fruscio
authors.forename: D
authors.initials: D
authors.lastname: Giuliani
authors.forename: R
authors.initials: R
authors.lastname: Milani
authors.forename: V
authors.initials: V
authors.lastname: Torri
authors.forename: M
authors.initials: M
authors.lastname: Broggini
authors.forename: M
authors.initials: M
authors.lastname: Marabese
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010984:Platinum / Q000008:administration & dosage / Q000009:adverse effects; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D054316:Biomarkers, Pharmacological; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D010984:Platinum; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C497206:MDM2 protein, human; C071447:ERCC1 protein, human