Pilger Diogo André, Lopez Patrícia Luciana da Costa, Segal Fábio, Leistner-Segal Sandra
Postgraduate Program in Medical Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Genomic Med. 2007;1(1-2):57-63. doi: 10.1007/s11568-007-9007-4. Epub 2007 May 25.
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.
蛋白质p53是一种参与细胞周期调控和细胞凋亡的肿瘤抑制因子。p53存在多种多态性，这些多态性可能会影响与蛋白质肿瘤抑制活性相关的重要区域。在所描述的多态性中，R213R和13949 g→a很少被研究，巴西人群的估计频率尚不可得。本研究的目的是调查巴西南部一组食管组织改变患者中这些多态性的基因型和等位基因频率及关联，并与对照组观察到的频率进行比较。对35例经上消化道内镜诊断并经活检证实有胃食管反流病（GERD）症状的患者进行了R213R多态性分析，对45例患者进行了13494 g→a多态性分析。两组均使用100名对照进行比较。对于一组有正常和病变组织的患者，还分析了杂合性缺失（LOH）情况。在分析的两个杂合样本中，有1例巴雷特食管（BE）患者显示R213R存在LOH，13494 g→a多态性有2例患者（食管炎和BE）存在LOH。我们还旨在构建一个与我们小组先前报道的R27P多态性一起共同分析的这两种多态性的单倍型。患者和对照组之间的等位基因和基因型分布没有显著差异。尽管使用了食管炎、贲门肠化生和BE样本，所有这些均为非肿瘤性病变，但我们可以得出结论，这些部位不代表GERD发展为BE和食管癌的遗传易感性标志物。需要进一步研究以调查已知易患食管癌的早期癌前病变的其他决定因素。
