title: Association between polymorphisms in xenobiotic detoxification-related genes with prognosis of epithelial ovarian cancer.
abstract: This study aimed to evaluate whether GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G and NQO2 c.-102A>C polymorphisms, involved in xenobiotic detoxification pathways, alter outcomes of epithelial ovarian cancer (EOC) patients. DNA from 84 EOC patients diagnosed at the University of Campinas Academic Hospital from January 1995 and July 2007 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival and overall survival (OS) of EOC patients was examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox proportional hazard ratio (HR) regression analyses. The significant results of Cox analyses were validated using a bootstrap resampling study (1000 replications). At 60 months of follow-up, lower OS was seen in patients with GSTT1 null genotype (50.0 vs. 76.7 %, P = 0.02) compared with the other genotype (Kaplan-Meier estimate). This outcome remained the same in univariate Cox analysis (HR 2.22, P = 0.02). After multivariate Cox analysis, patients with GSTT1 null (HR 2.11, P = 0.04, P bootstrap = 0.04) and NQO2 AA (HR 2.13, P = 0.03, P bootstrap = 0.04) genotypes were under greater risks of progressing to death when compared with those with others genotypes. Our data suggest, for the first time, that inherited abnormalities in xenobiotic detoxification pathway related to GSTT1 and NQO2 c.-102A>C polymorphisms act as independent prognostic factors for OS of EOC patients.
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors: Juliana
authors: J
authors: Carron
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors: Angelo Borsarelli Carvalho
authors: AB
authors: Brito
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors: Ana Carolina Mourão
authors: AC
authors: Torelli
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors: Cristiane
authors: C
authors: Oliveira
authors: Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 101, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-881, Brazil.
authors: Sophie Françoise Mauricette
authors: SF
authors: Derchain
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors: Carmen Silvia Passos
authors: CS
authors: Lima
authors: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil. gutolour@fcm.unicamp.br.
authors: Gustavo Jacob
authors: GJ
authors: Lourenço
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011808:Quinone Reductases / Q000235:genetics*; D015262:Xenobiotics / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D011808:Quinone Reductases; D015262:Xenobiotics; C419642:NRH - quinone oxidoreductase2; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human
keywords: Epithelial ovarian cancer; GSTT1; NQO2; Prognosis; Single nucleotide polymorphism