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

Abstract

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.

TP53 Polymorphisms in Sporadic North Indian Breast Cancer Patients

“…Thus, there was no association of p.R213R polymorphism with breast cancer similar to reports in ovarian (Mazars et al, 1992), Barretts esophagus patients (Pilger et al, 2007) and different tumors (Iihan et al, 1995).…”

Analysis of TP53 Polymorphisms in North Indian Sporadic Esophageal Cancer Patients

“…Similarly, no association of r.13494g>a polymorphism has been reported in Brazilian Barretts esophagus patients (Pilger et al, 2007). Apart from esophageal cancer, no association of this polymorphism was documented in Caucasians breast (Mavridou et al, 1998), Israeli ovarian (Yair et al, 2000) and Indian cervical (Mitra et al, 2005) cancer patients.…”

“…No association of p.R213R polymorphism has been reported in ovarian (Mazars et al, 1992) and Barretts esophagus (Pilger et al, 2007) patients.…”

“…Though, published studies substantially lack information on p.R213R polymorphism in EC. No association of p.R213R polymorphism with cancer risk has been observed in Brazilian Barretts esophagus patients (Pilger et al, 2007). Intronic polymorphisms of TP53 gene may influence coding-region sequence alterations that results in increase of a deleterious phenotype (Malkinson and You, 1994).…”

“…The r.13494g>a has been studied in various cancers including ovarian (Wang-Gohrke et al, 1999;Yair et al, 2000), head and neck (Mitra et al, 2003;Chen et al, 2007), esophageal (Pilger et al, 2007), breast (Peller et al, 1995;Sjalander et al, 1996;Weston et al, 1997;Akkiprik et al, 2009;Singh et al, 2008;Hrstka et al, 2009), cervical (Mitra et al, 2004), colorectal (Mammano et al, 2009), lung (Biros et al, 2001;, prostate cancer DOI:http://dx.doi.org/10.7314/APJCP.2014.15.19.8413 TP53 Polymorphisms in North Indian Esophageal Cancer Patients into the etiology of this cancer and provide targets for the future development of therapeutic approaches.…”