BRCA2 germline mutations in familial pancreatic carcinoma
BRCA2 germline mutations in familial pancreatic carcinoma
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DOI：
10.1093/jnci/95.3.214
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发表时间：
2003-02-05
影响因子：
10.3
通讯作者：
Bartsch, DK
中科院分区：
文献类型：
--
作者：
Hahn, SA;Greenhalf, B;Bartsch, DK
背景：虽然高达10%的胰腺癌病例可能有遗传成分，但家族性胰腺癌并未与任何特定基因的缺陷有关。一些研究表明，乳腺癌易感基因BRCA2胚系突变的家庭患乳腺癌和卵巢癌的风险增加，患胰腺癌的风险略有增加。为了更详细地研究这些关系，我们检查了BRCA2胚系突变是否与家族性胰腺癌相关。方法：我们确定了26个欧洲家系，其中至少有两个一级亲属被组织学确诊为胰腺导管腺癌。我们对从参与试验的家庭成员的外周血淋巴细胞中分离的基因组DNA进行了测序，以确定BRCA2的种系突变。结果：3个家系(12%，确切95%可信区间[CI]=2%至30%)携带BRCA2基因的生殖系移码突变，预测导致BRCA2蛋白被截断。另外两个家族含有之前被指定为BRCA2非分类变体的突变。因此，在我们的研究中，19%的家系(确切的95%CI=7%到39%)要么有BRCA2的移码突变，要么有未分类的变异。在我们的研究中，没有一个家族符合家族性乳腺癌或卵巢癌的标准。结论：我们的数据支持BRCA2胚系突变在家族性胰腺癌家族亚群中的重要作用。BRCA2突变分析应该包括在至少有两个一级亲属受胰腺导管腺癌影响的家庭的分子遗传学测试和咨询策略中。
Background: Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer. Methods: We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2. Results: Three (12%, exact 95% confidence interval [CI] = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer. Conclusions: Our data support an important role for BRCA2 germline mutations in a sub-population of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.