title: Genotype and Haplotype Analyses of TP53 Gene in Breast Cancer Patients: Association with Risk and Clinical Outcomes.
abstract: Variations in the TP53 gene have been suggested to play a role in many cancers, including breast. We previously observed an association between TP53 haplotypes based on four polymorphisms (rs17878362, rs1042522, rs12947788, and rs17884306) and the risk of colorectal and pancreatic cancer. Based on these results, in the present study, we have investigated the same polymorphisms and their haplotypes in 705 breast cancer cases and 611 healthy controls in relation to the disease risk, histopathological features of the tumor and clinical outcomes. In comparison to the most common haplotype A1-G-C-G, all the other identified haplotypes were globally associated with a significantly decreased breast cancer risk (P = 0.006). In particular, the A2-G-C-G haplotype was associated with a marked decreased risk of breast cancer when compared with the common haplotype (P = 0.0001). Moreover, rs1042522 in patients carrying the GC genotype and receiving only the anthracycline-based chemotherapy was associated with both overall and disease-free survival (recessive model for overall survival HR = 0.30 95% CI 0.11-0.80, P = 0.02 and for disease-free survival HR = 0.42 95% CI 0.21-0.84, P = 0.01). Present results suggest common genetic features in the susceptibility to breast and gastrointestinal cancers in respect to TP53 variations. In fact, similar haplotype distributions were observed for breast, colorectal, and pancreatic patients in associations with cancer risk. Rs1042522 polymorphism (even after applying the Dunn-Bonferroni correction for multiple testing) appears to be an independent prognostic marker in breast cancer patients.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University, Prague, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Vymetalkova
authors.affiliation: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.affiliation: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Kunicka
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Jiraskova
authors.affiliation: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Brynychova
authors.affiliation: Human Genetics Foundation, Turin, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.affiliation: Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Novosadova
authors.affiliation: Department of General Biology and Genetics, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Zdena
authors.initials: Z
authors.lastname: Polivkova
authors.affiliation: Department of Oncology, University Hospital Motol, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kubackova
authors.affiliation: Department of Oncosurgery, MEDICON, Prague, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Kozevnikovova
authors.affiliation: Department of Radiotherapy and Oncology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Ambrus
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University, Prague, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Human Genetics Foundation, Turin, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors