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.

Department of General Biology and Genetics 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Oncology University Hospital Motol Prague Czech Republic

Department of Oncosurgery MEDICON Prague Czech Republic

Department of Radiotherapy and Oncology 3rd Faculty of Medicine Charles University Prague Czech Republic

Human Genetics Foundation Turin Italy

Institute of Biotechnology Academy of Sciences of the Czech Republic Prague Czech Republic

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic; Human Genetics Foundation Turin Italy

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic; Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Toxicogenomics Unit National Institute of Public Health Prague Czech Republic

Toxicogenomics Unit National Institute of Public Health Prague Czech Republic; 3rd Faculty of Medicine Charles University Prague Czech Republic

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