Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers
Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers
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DOI：
10.1016/s0959-8049(03)00368-x
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发表时间：
2003-07-01
影响因子：
8.4
通讯作者：
Nardone, G
中科院分区：
文献类型：
--
作者：
Rocco, A;Staibano, S;Nardone, G
为了确定一组家族性胃癌（FGC）亲属中胃癌前病变和粘膜遗传改变的患病率，我们研究了一个跨越两代的亲属。创始人、女儿和侄女因胃癌（GC）接受了手术；创始人的一个儿子和另外两个女儿，患有慢性消化不良。对所有受试者的胃粘膜样本进行病理特征、幽门螺杆菌感染、微卫星（MIN）和染色体（CIN）不稳定性分析。在2例年轻的癌症患者中发现了mp53和c-myc的过表达和细胞质β -连环蛋白的脱位。所有胃癌和胃炎患者E-cadherin表达正常，min阴性。非整倍性是所有胃癌病例的特征，在三个“危险”亲属的胃活检中，有两个存在混合的整倍体和非整倍体细胞群。这两名受试者，其中一人患有严重的活动性胃炎，胃mp53和c-myc表达，为caga阳性幽门螺杆菌感染。DNA非整倍体、p53和c-myc的表达在幽门螺杆菌根除后消失。在这个FGC集群中，仅在存在幽门螺杆菌感染的一级亲属（3例患者）中发现遗传异常（2例幽门螺杆菌阳性对1例幽门螺杆菌阴性），这支持了一种假设，即除了遗传谱的影响外，FGC可能至少部分地由幽门螺杆菌感染的家族内集群介导。(C) 2003 Elsevier Ltd.版权所有。
To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosornal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, Lit least partly, mediated by intrafamilial clustering of H. pylori infection. (C) 2003 Elsevier Ltd. All rights reserved.