Familial pancreatic cancer
Familial pancreatic cancer
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DOI：
10.1023/a:1008345021197
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发表时间：
1999-01-01
影响因子：
50.5
通讯作者：
Kern, SE
中科院分区：
文献类型：
--
作者：
Hruban, RH;Petersen, GM;Kern, SE
背景：多年来，轶事病例报告表明胰腺癌在某些家庭中聚集。方法：最近的两项进展证实事实确实如此。首先，大型登记处，例如约翰·霍普金斯大学的国家家族性胰腺肿瘤登记处 (NFPTR)，已经确定了许多家庭，其中多名家庭成员被诊断患有胰腺癌。因此，现在可以以前所未有的规模研究胰腺癌的遗传模式。其次，分子遗传学技术的进步使得测试这些家族成员的已知候选致癌基因的种系突变成为可能。结果，在一些家庭中发现了导致胰腺癌家族聚集的一些基因改变。结果：NFPTR 已登记了 362 个家庭，其中至少一名家庭成员已被诊断患有胰腺癌。其中包括 151 个家庭，其中至少有两名一级亲属被诊断患有胰腺癌。对这些家庭的分析表明，即使是这些家庭患者的二级亲属，患胰腺癌的风险也会增加。此外，已经对许多表现出癌症聚集的亲属进行了已知致癌基因的种系突变测试。研究表明，BRCA2 种系突变会导致乳腺癌和胰腺癌，p16 种系突变会导致黑色素瘤和胰腺癌（FAMMM 综合征），STK11/LKB1 基因突变会导致黑斑息肉综合征 (PJS) 患者罹患胰腺癌。结论：胰腺癌在一些家族中聚集，胰腺癌患者的亲属本身患胰腺癌的风险增加。胰腺癌家族聚集的遗传基础已被证明是其中一些家族中已知致癌基因的种系突变。
Background: For many years anecdotal case reports have suggested that pancreatic cancer aggregates in some families.Methods: Two recent advances have established that this is in fact the case. First, large registries, such as the National Familial Pancreas Tumor Registry (NFPTR) at Johns Hopkins, have identified a number of families in which multiple family members have been diagnosed with pancreatic cancer. As a result, the patterns of inheritance of pancreatic cancer can now be studied on a scale not possible before. Second, advances in molecular genetic techniques make it possible to test members of these families for germline mutations in known candidate cancer causing genes. As a result, some of the genetic alterations responsible for the familial aggregation of pancreatic cancer have been identified in some families.Results: The NFPTR has enrolled 362 families in which at least one family member has been diagnosed with pancreatic cancer. These include 151 families in which at least two first-degree relatives have been diagnosed with pancreatic cancer. Analysis of these families has revealed that even second-degree relatives of patients from these families are at increased risk of developing pancreatic cancer. In addition, a number of kindreds which exhibit aggregation of cancer have been tested for germline mutations in known cancer causing genes. Germline mutations in BRCA2 have been shown to predispose to both breast and pancreatic cancer, germline mutations in p16 to melanoma and pancreatic cancer (the FAMMM syndrome), and genetic mutations in STK11/LKB1 to pancreatic cancer in patients with the Peutz-Jeghers Syndrome (PJS).Conclusions: Pancreatic cancer aggregates in some families, and relatives of patients with pancreatic cancer have an increased risk of developing pancreatic cancer themselves. The genetic basis for the familial aggregation of pancreatic cancer has been shown to be germline mutations in known cancer causing genes in some of these families.