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首页> 外文期刊>American Journal of Physiology >Age-associated loss of heterozygosity of tumor suppressor genes in the gastric mucosa of humans.
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Age-associated loss of heterozygosity of tumor suppressor genes in the gastric mucosa of humans.

机译：与年龄相关的人胃粘膜中抑癌基因杂合性的丧失。

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摘要

The current study is based on the hypothesis that aging predisposes gastric mucosa to carcinogenesis through altered expression and/or mutations of genes involved in cell growth. To test this hypothesis, we investigated the age-associated changes in mutation of adenomatous polyposis coli (APC), deleted in colorectal cancer (DCC), p53, and K-ras genes in the gastric mucosa of 19 healthy subjects of varying ages (25-91 yr). Specifically, we studied the loss of heterozygosity (LOH) of these genes in cardia, body, and antrum of the stomach. We observed that 3 of 19 subjects (16%) over 60 yr of age show LOH of at least one of the tumor suppressor genes. Among the subjects over 60 yr of age, the incidence of LOH is 38% (3/8). Two of three subjects had mutations in more than one tumor suppressor gene. In all three affected subjects, mutation in APC, DCC, or p53 was located mainly in the body of the stomach, suggesting increased susceptibility of this region to neoplastic changes. However, no LOH of K-ras was observed in these subjects. Our observation that subjects over 60 yr of age show mutation in one or more of the tumor suppressor genes suggests an age-related increase in predisposition of the stomach to neoplasia.
机译：当前的研究基于这样的假设：衰老使胃粘膜易于通过改变与细胞生长相关的基因的表达和/或突变而致癌。为了验证这一假设，我们调查了19名不同年龄健康受试者胃黏膜中结肠直肠息肉病（APC）突变，大肠癌（DCC），p53和K-ras基因缺失的突变与年龄相关的变化（25 -91年）。具体来说，我们研究了card门，身体和胃窦中这些基因的杂合性（LOH）丧失。我们观察到年龄超过60岁的19位受试者中有3位（16％）显示出至少一种肿瘤抑制基因的LOH。在60岁以上的受试者中，LOH的发生率为38％（3/8）。三分之二的受试者中有一个以上的抑癌基因突变。在所有三个受影响的受试者中，APC，DCC或p53的突变主要位于胃体中，表明该区域对肿瘤变化的敏感性增加。然而，在这些受试者中未观察到K-ras的LOH。我们观察到超过60岁的受试者显示一种或多种肿瘤抑制基因发生突变，这表明与胃相关的肿瘤易感性与年龄有关。

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