title: XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma.
abstract: This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients. DNA from 237 CM patients seen at the University of Campinas Teaching Hospital from April 2000 to February 2014 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival (PFS) and overall survival (OS) of CM patients were examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox regression analyses. At 60 months of follow-up, shorter PFS and OS were seen in patients with XPF CC genotype (48.9 vs. 66.7 %, P = 0.002; 77.9 vs. 83.5 %, P = 0.006, respectively) and XPF CC + TP53 ArgArg (43.6 vs. 65.9 %, P = 0.007; 71.6 vs. 84.8 %, P = 0.006, respectively) compared with those with remaining genotypes (Kaplan-Meier estimates). Patients with XPF CC (hazard ratio (HR) 2.45, P = 0.002; HR 3.77, P = 0.005) and XPF CC + TP53 ArgArg (HR 2.67, P = 0.009; HR 4.04, P = 0.03) genotypes had more chance to present tumor progression in univariate and multivariate analyses, whereas patients with XPF CC (HR 2.78, P = 0.009) and XPF CC + TP53 ArgArg (HR 3.84, P = 0.01) genotypes were under greater risk of progressing to death in univariate analysis, compared with those with the remaining genotypes. The data suggest, for the first time, that inherited abnormalities in DNA repair pathway related to XPF 30028C and TP53 Arg72Pro polymorphisms act as prognostic factors for PFS and OS of CM patients.
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil.
authors.forename: Gabriela Vilas Bôas
authors.initials: GV
authors.lastname: Gomez
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil.
authors.forename: José Augusto
authors.initials: JA
authors.lastname: Rinck-Junior
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil.
authors.forename: Aparecida Machado
authors.initials: AM
authors.lastname: de Moraes
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil.
authors.forename: Gustavo Jacob
authors.initials: GJ
authors.lastname: Lourenço
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Barão Geraldo, São Paulo, 13083-970, Campinas, Brazil. carmenl@fcm.unicamp.br.
authors.forename: Carmen Silvia Passos
authors.initials: CS
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C095888:xeroderma pigmentosum group F protein; C086984:XPC protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
keywords: Cutaneous melanoma; DNA repair; Genetic polymorphism; Survival