Family history of pancreatic cancer in a high-risk cancer clinic: implications for risk assessment.
Family history of pancreatic cancer in a high-risk cancer clinic: implications for risk assessment.
复制标题
DOI：
10.1007/s10897-008-9154-3
复制
发表时间：
2008-08-01
影响因子：
1.9
通讯作者：
Olopade, Olufunmilayo I
中科院分区：
文献类型：
--
作者：
Hall, Michael J;Dignam, James J;Olopade, Olufunmilayo I
详细的家族史是癌症风险评估的关键因素。胰腺癌(PC)在近亲家庭成员中的相对重要性，特别是在遗传性乳腺卵巢综合征(HBOS)中，还没有明确的定义。我们使用病例对照设计来调查PC家族史对癌症风险评估的重要性。病例和对照家系来自芝加哥大学癌症风险数据库(1994-2005)。家系分析了个人和家族癌症的临床资料。病例包括所有新的受试者(先证者)，报告有一位近亲(一级或二级)患有PC。对照包括在每个病例之前和之后登记在数据库中的先证者(即每个病例有两个对照)。在1,231个家系中，先证者报告了103个PC，隶属于87个独特的家系。许多先证者报告了多发性或早发性PC：三分之一(28/87)的病例家系符合家族性PC综合征的标准[或=2个患有PC的一级亲属(n=10)或PC诊断为<；或=50(n=18)]。在这些家庭中，大多数(75%)同时符合遗传性乳腺卵巢综合征(HBOS)的标准。由于家族史与HBOS一致，29个病例家系和55个对照家系中至少有一人接受了BRCA1/2基因检测。在病例家系中，29个家系中有19个(66%)有BRCA1/2突变，而对照组中有16个(29%)发生突变。PC家族史与BRCA1/2突变显著相关(OR 3.78，1.32~10.9)。这一点估计得到了加强，但在受测家庭中非德系犹太人家庭中的精确度较低(OR 6.03，1.68-22.14)。在高危人群中，PC的家族史虽然很少被报道，但在临床上是有意义的。在HBOS的风险评估中，确定PC的家族史应该强烈地增加对未识别的BRCA1/2突变的怀疑。
Detailed family history is a critical element of cancer risk assessment. The relative importance of pancreatic cancer (PC) in a close family member, particularly in hereditary breast-ovarian syndrome (HBOS), is not clearly defined. We use a case-control design to investigate the importance of a family history of PC to cancer risk assessment. Case and control families were identified from the University of Chicago Cancer Risk database (1994-2005). Pedigrees were analyzed for personal and familial clinical cancer data. Cases included all new subjects (probands) reporting a close relative (first or second degree) with PC. Controls included the probands enrolled in the database immediately prior to and subsequent to each case (i.e. two controls for each case). From 1,231 pedigrees, 103 PC were reported by the proband in 87 unique families. Many probands reported multiple or early-onset PCs: one third (28/87) of case families met criteria for a familial PC syndrome [> or =2 first-degree relatives with PC (n = 10) or PC diagnosed < or =50 (n = 18)]. Of these families, the majority (75%) concurrently met criteria suggestive of hereditary breast-ovarian syndrome (HBOS). Because of a family history consistent with HBOS, at least one individual from each of 29 case and 55 control families underwent genetic testing for BRCA1/2. Among case families, 19 of 29 (66%) had a BRCA1/2 mutation compared with 16 of 55 (29%) controls. A significant association between family history of PC and a BRCA1/2 mutation was seen (OR 3.78, 1.32-10.9). This point estimate was strengthened but less precise in the non-Ashkenazi Jewish subset of tested families (OR 6.03, 1.68-22.14). In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation.