title: The 5'UTR variant of ERCC5 fails to influence outcomes in ovarian and lung cancer patients undergoing treatment with platinum-based drugs.
abstract: The common polymorphic variant in the 5' untranslated region of the excision repair cross-complementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal ERCC5 expression and its ability to be synthesized following DNA damage. This variant was reported to affect response to platinum therapy in a cohort of patients with pediatric ependymoma. The role of this variant was investigated in two cohorts of cancer patients, specifically in non-small-cell lung cancer (NSCLC) patients (N = 137) and in epithelial ovarian carcinoma (EOC) patients (N = 240), treated in first-line with platinum-based compounds. Differently from what reported for pediatric ependymoma, the analysis of the polymorphism in NSCLC patients cohort was not able to detect any difference among patients harboring different genotypes both in progression free survival (HR = 0.93; 95%CI 0.64-1.33; p-value = 0.678) and overall survival (HR = 0.90; 95%CI 0.62-1.33; p-value = 0.625). These data were corroborated in a EOC patients cohort, where similar progression free survival (HR = 0.91; 95% CI 0.67-1.24; p-value = 0.561) and overall survival (HR = 0.98; 95% CI 0.71-1.35; p-value = 0.912) were found for the different genotypes. These data, obtained in appropriately sized populations, indicate that the effect of this ERCC5 polymorphism is likely to be relevant only in specific tumors.
authors.affiliation: Laboratory of Methodology For Clinical Research, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Guffanti
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caiola
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Damia
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Garassino
authors.affiliation: Oncology Department, Ospedale Fatebenefratelli e Oftalmico, 20121 Milan, Italy.
authors.forename: Sheila
authors.initials: S
authors.lastname: Piva
authors.affiliation: Clinic of Obstetrics and Gynecology, University of Milan Bicocca, San Gerardo Hospital, 20900 Monza, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ceppi
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
mesh_terms: D020121:5' Untranslated Regions; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000071184:Pharmacogenomic Variants; D010984:Platinum / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D020121:5' Untranslated Regions; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D010984:Platinum; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5