Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer

Abstract

ABSTRACT. The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.

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].…”

“…Similarly, a Mexican study reported a significant association between the c.1196A>G (rs25487) variant of the XRCC1 gene and breast cancer risk [121]. Variants in TP53 , which is an important gene in DNA-repair related pathways [140], were reported in Brazilian populations [83,84,85,114,141,142,143,144,145]. Four case-control studies assessed the rs1042522 (c.215C>A) variant, reporting negative results.…”

Association between TP53 codon 72 G>C Polymorphism and Thyroid Carcinoma Risk: An Up-to-Date Meta-Analysis

“…Since the dysfunction of cell cycle can result in the development of cancer, genetic mutations in the p53 gene are suggested to alter host's susceptibility to thyroid cancer [25]. There are several common single nucleotide polymorphisms in the p53 gene, and P53 codon 11, 47, 72, and 248 polymorphisms are the three most studied ones [26]. p53 codon 72 polymorphism is a G to C substitution at exon 6, which further results in an amino acid change from Arg to Pro [27].…”

Landscape of Germline Mutations in DNA Repair Genes for Breast Cancer in Latin America: Opportunities for PARP-Like Inhibitors and Immunotherapy

“…Considering the inclusion criteria, 81 studies were selected for extensive analysis [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,…”