Assessment of changes in the brca2 and p53 genes in breast invasive ductal carcinoma in northeast Brazil

Abstract

BackgroundBRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.ResultsBRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.ConclusionsThere was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.

Association of p53 rs1042522, MDM2 rs2279744 and p21 rs1801270 polymorphisms with retinoblastoma risk and invasion in a Chinese population

“…Therefore, our findings may be useful in the near future for the promotion of prevention strategies guided by the patient’s genotype because the p53 rs1042522 GC genotype was associated with reduced RB invasion (over-dominant model). However, contrary to our finding, the GC genotype of rs1042522 showed a “heterozygote disadvantage” in which the heterozygote displayed an increased risk of metastasis in breast-invasive ductal carcinoma, based on a study conducted in northeast Brazil 43 . Although two wild-type alleles of rs1042522 have different potentials in binding components of the transcriptional machinery, activating transcription, inducing apoptosis, and repressing cancer cells, recent studies demonstrate that rs1042522 could also be associated with cancer through an epigenetic mechanism, including RNAi suppression 44 and DNA methylation 45 .…”

Genetic Epidemiology of Breast Cancer in Latin America

“…The heterozygous frequency ranges between 40 and 60% and the frequency of the homozygous genotype is ~10%. These frequencies are also similar to the frequencies in the healthy population [141,142,143,144]. Even though the prevalence of this mutation is variable across different populations, these results are similar to the average frequencies observed worldwide [146].…”

Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry

“…However, Mikeska et al (2013) found little evidence of PALB2 methylation in high-grade serous ovarian cancer using a methylation-sensitive high-resolution melting assay, and Poumpouridou et al (2016) were unable to detect PALB2 promoter methylation in a series of 91 breast cancers [10,11]. Studies of BRCA2 and CHEK2 have found no evidence for regulation or silencing via methylation [12,13]. …”