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.

A Novel Mutation-BRCA1 Associated Hereditary Haplotype of Intragenic Markers of BRCA1 Gene in a Family with History of Breast Cancer

“…Previous study in woman suffer from breast cancer suggested that One haplotype of the ESR2 gene was associated with breast cancer risk (Cox et al, 2008). Also, analysis in TP53 gene identified a haplotype that associated with a significantly decreased breast cancer risk (Vymetalkova et al, 2015). Our Identified variation (IVS17-21delA), probably, associated with an increased risk of breast cancer.…”

TP53 (RS1042522) Polymorphism In Breast Cancer

“…It was also found that patients with GG genotype possibly response to radiation or chemotherapy more properly than other variants. Additionally, studies on Finnish, Spanish and Japanese groups have supported that patients with CC genotype have less survival than patients carrying other genotypes 9 .…”

“…For further studies, TP53 (rs1042522) polymorphism may be associated with other genetic factors because p53 interacts with various proteins that play role in programmed cell death 5,9 . For instance, it has been evaluated that some fibroblast growth factor receptor 2(FGFR2) gene polymorphisms are 3 0 associated with breast cancer and FGFR2 gene accomplishes its function in a p53-dependent manner.…”

“…P53 has a regulatory function in repair of DNA damage, cell apoptosis, cell senescence and cell cycle control through inhibition of cell division when irretrievable DNA damage occurs 5,7,8 . Beside DNA damage, it has a central role in stress responses such as hypoxia, metabolite stress and oncogene activation to protect genomic stability 9 . Also, the high incidence rate of p53 inactivation in human cancers emphasizes the significance of its tumour suppressor function.…”

Análise da expressão de RNAs longos não codificantes em tumores metastáticos de câncer de mama

“…Acredita-se que o CDIS seja o precursor do carcinoma ductal invasivo -aquele onde há invasão do tecido adjacentesendo a perda da organização da camada celular mioepitelial e da membrana basal os critérios que definem a transição de um para o outro (Hu, et al, 2008). De uma forma geral, o prognóstico do carcinoma de mama é influenciado pelo estágio do tumor, grau, superexpressão do homólogo 2 do oncogene viral de leucemia eritroblástica aviária v-erb-b2 (ERBB2), e receptores hormonais (Vymetalkova et al, 2015).…”