Familial gastric cancer:: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations
Familial gastric cancer:: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations
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DOI：
10.1093/carcin/20.6.1127
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发表时间：
1999-06-01
期刊：
影响因子：
4.7
通讯作者：
Yokota, J
中科院分区：
文献类型：
--
作者：
Shinmura, K;Kohno, T;Yokota, J
胃癌常发生于遗传性非息肉病性结直肠癌（HNPCC）和Li-Fraumeni综合征（LFS）的家族成员中，最近在家族性胃癌的一个子集中发现了E-cadherin的生殖细胞突变。因此，通过回顾3632例胃癌患者的系谱树，招募了具有聚集性胃癌的家族。招募此类家庭的标准如下：至少有三名亲属患有胃癌，其中一名应为其他两人的一级亲属;至少连续两代人应受到影响;其中一名亲属应在50岁之前被诊断出胃癌，31例病例（0.9%）符合所有这三个标准。在31个家系中，18个家系中仅有胃癌患者，无符合HNPCC或LFS临床标准的家系。29个先证者有石蜡包埋组织，13个先证者成功提取DNA进行分子生物学分析。RER表型检测在3例（23%），而生殖系p53突变检测在13例。在三种弥漫型中的一种和10种肠型中均未检测到种系E-钙粘蛋白突变，然而，在前体序列中检测到导致甘氨酸被瓦尔取代的突变。因此，虽然胃癌的家族聚集性发生在类似于1%的胃癌患者中，但DNA错配修复、p53和E-钙粘蛋白基因的种系突变并不显著有助于这种聚集。
Gastric cancer frequently occurs in family members with hereditary non-polyposis colorectal cancer (HNPCC) and Li-Fraumeni syndrome (LFS) and germline E-cadherin mutations were recently identified in a subset of familial gastric cancers. Thus, families with an aggregation of gastric cancers were recruited by reviewing the genealogical trees of 3632 patients with gastric cancer. The criteria for recruiting such families were the following: at least three relatives should have gastric cancer and one of them should be a first degree relative of the other two; at least two successive generations should be affected; in one of the relatives gastric cancer should be diagnosed before age 50, Thirty-one cases (0.9%) fitted all three of these criteria. There were only gastric cancer patients in 18 of the 31 families and there were no families that fitted clinical criteria of HNPCC or LFS, Paraffin-embedded tissues were available in 29 probands and DNA was successfully isolated for molecular analyses in 13 probands. RER phenotype was detected in three (23%) cases, whereas germline p53 mutations were detected in none of 13 cases. A germline E-cadherin mutation was detected in one of three diffuse types and none of 10 intestinal types, however, a mutation resulting in the replacement of Gly by Val was detected in the precursor sequence. Thus, although familial clustering of gastric cancer occurs in similar to 1% of gastric cancer patients, germline mutations of the DNA mismatch repair, p53 and E-cadherin genes do not significantly contribute to such a clustering.