An intronic variant in the TP53 gene in a Brazilian woman with breast cancer

Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. There are several polymorphisms reported for p53 which can affect important regions involved in protein tumor suppressor activity. Amongst the polymorphisms described, R213R and 13949 g→a are rarely studied, with an estimate frequency not yet available for the Brazilian population. The purpose of this study was to investigate the genotype and allele frequencies and associations of these polymorphisms in a group of patients with altered esophageal tissue from South Brazil and compare with the frequency observed for a control population. A total of 35 patients for R213R and 45 for 13494 g→a polymorphisms analysis with gastroesophageal reflux disease (GERD) symptoms diagnosed by upper digestive endoscopy and confirmed by biopsy were studied. For both groups, 100 controls were used for comparison. Loss of heterozygosity (LOH) was also analyzed for a selected group of patients where normal and affected tissue was available. There was one patient with Barrett’s Esophagus (BE) showing LOH for R213R out of two heterozygous samples analyzed and two patients (esophagitis and BE) for 13494 g→a polymorphism. We also aimed to build a haplotype for both polymorphisms collectively analyzed with R27P polymorphism, previously reported by our group. There were no significant differences in allele and genotype distribution between patients and controls. Although using esophagitis, intestinal metaplasia of the cardia and BE samples, all non-neoplastic lesions, we can conclude that these sites do not represent genetic susceptibility markers for the development and early progression of GERD to BE and esophageal cancer. Additional studies are required in order to investigate other determiners of early premalignant lesions known to predispose to esophageal cancer.

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“…2000; Lacerda et al. 2005). Hence, we also carried out a joint analysis of the three polymorphisms described by means of a haplotype.…”

Section: Discussionmentioning

confidence: 99%

“…Identification of these alterations may help select patients with a higher risk of developing cancer, allowing optimization of treatments (Lacerda et al. 2005). …”

Section: Discussionmentioning

confidence: 99%

Analysis of R213R and 13494 g→a polymorphisms of the p53 gene in individuals with esophagitis, intestinal metaplasia of the cardia and Barrett’s Esophagus compared with a control group

Pilger

Lopez

Segal³

et al. 2007

HUGO J

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“…Although both variants are morphologically wild-type, the Pro/Pro genotype is less effective in suppressing cellular transformation 15. Several studies have reported that the p53 codon 72 polymorphism may be associated with tumor susceptibility to a variety of cancers recently 16-18. The GSTP1 gene displays a polymorphism, an A>G change at codon 105, resulting in an Ile-to-Val substitution (rs1695), which alters the enzymatic activity of the protein 18.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have reported that the p53 codon 72 polymorphism may be associated with tumor susceptibility to a variety of cancers recently 16-18. The GSTP1 gene displays a polymorphism, an A>G change at codon 105, resulting in an Ile-to-Val substitution (rs1695), which alters the enzymatic activity of the protein 18. This has been suggested as a putative high-risk genotype in various cancers 19.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - A Meta-Analysis

Zhao¹,

Wang²,

Shan³

et al. 2010

Int. J. Med. Sci.

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A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity.In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.

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“…26). This polymorphism may be associated with tumor susceptibility to a variety of cancers (27)(28)(29). The polymorphism of the p53 gene at codon 72 is considered as a risk factor of the human papillomavirusassociated cervical neoplasia and ESCC (30,31).…”

Section: Introductionmentioning

confidence: 99%

Dietary Selenium Intake and Genetic Polymorphisms of the GSTP1 and p53 Genes on the Risk of Esophageal Squamous Cell Carcinoma

Cai

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Few studies have assessed potential effect modifications by polymorphisms of susceptibility genes on the association between selenium intake and esophageal squamous cell carcinoma (ESCC). We studied the joint effects of dietary selenium and the GSTP1 and p53 polymorphisms on ESCC risk in a population-based case-control study with 218 ESCC cases and 415 controls in Taixing City, China. Dietary selenium intake was estimated from a food frequency questionnaire with 97 food items. GSTP1 and p53 polymorphisms were detected by RFLP-PCR assays. Logistic regression analyses were done to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Reduced ESCC risk was observed among individuals in the highest quartile of dietary selenium intake (adjusted OR, 0.31; 95% CI, 0.13-0.70) with a dose-dependent gradient (P trend = 0.01).

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An intronic variant in the TP53 gene in a Brazilian woman with breast cancer

Cited by 5 publications

References 12 publications

Analysis of R213R and 13494 g→a polymorphisms of the p53 gene in individuals with esophagitis, intestinal metaplasia of the cardia and Barrett’s Esophagus compared with a control group

Analysis of R213R and 13494 g→a polymorphisms of the p53 gene in individuals with esophagitis, intestinal metaplasia of the cardia and Barrett’s Esophagus compared with a control group

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - A Meta-Analysis

Dietary Selenium Intake and Genetic Polymorphisms of the GSTP1 and p53 Genes on the Risk of Esophageal Squamous Cell Carcinoma

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