Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Cancer. 2012 Jan 15;118(2):493-9. doi: 10.1002/cncr.26191. Epub 2011 May 19.
Germline mutations in the BRCA2 cancer susceptibility gene are associated with an increased risk of pancreatic cancer (PC). Breast-pancreas cancer families with BRCA1 mutations have also been observed. The influence of a family history (FH) of PC on BRCA mutation prevalence in patients with breast cancer (BC) is unknown.
A clinical database review (2000-2009) identified 211 Ashkenazi Jewish (AJ) BC probands who 1) underwent BRCA1/2 mutation analysis by full gene sequencing or directed testing for Ashkenazi founder mutations (BRCA1: 185delAG and 5382insC; BRCA2: 6174delT) and 2) had a FH of PC in a first-, second-, or third-degree relative. For each proband, the pretest probability of identifying a BRCA1/2 mutation was estimated using the Myriad II model. The observed-to-expected (O:E) mutation prevalence was calculated for the entire group.
Of the 211 AJ BC probands with a FH of PC, 30 (14.2%) harbored a BRCA mutation. Fourteen (47%) of the mutations were in BRCA1 and 16 (53%) were in BRCA2. Patients diagnosed with BC at age ≤ 50 years were found to have a higher BRCA1/2 mutation prevalence than probands with BC who were diagnosed at age > 50 years (21.1% vs 6.9%; P = .003). In patients with a first-, second-, or third-degree relative with PC, mutation prevalences were 15.4%, 15.3%, and 8.6%, respectively (P = .58). In the overall group, the observed BRCA1/2 mutation prevalence was 14.2% versus an expected prevalence of 11.8% (O:E ratio, 1.21; P = .15).
BRCA1 and BRCA2 mutations are observed with nearly equal distribution in AJ breast-pancreas cancer families, suggesting that both genes are associated with PC risk. In this population, a FH of PC was found to have a limited effect on mutation prevalence.
BRCA2 癌症易感性基因的种系突变与胰腺癌（PC）风险增加相关。已经观察到带有 BRCA1 突变的乳腺癌-胰腺肿瘤家族。家族史（FH）对乳腺癌（BC）患者 BRCA 突变发生率的影响尚不清楚。
对临床数据库进行回顾（2000-2009 年），确定了 211 名阿什肯纳兹犹太裔（AJ）BC 先证者，他们 1）通过全基因测序或针对阿什肯纳兹创始人突变（BRCA1：185delAG 和 5382insC；BRCA2：6174delT）的定向测试进行了 BRCA1/2 突变分析，2）在一级、二级或三级亲属中存在 PC 的 FH。对于每个先证者，使用 Myriad II 模型估计识别 BRCA1/2 突变的术前概率。计算整个组的观察到的预期（O：E）突变发生率。
在 211 名 AJ BC 先证者中，有 FH 的 PC 中有 30 名（14.2%）携带 BRCA 突变。14 个（47%）突变发生在 BRCA1 中，16 个（53%）突变发生在 BRCA2 中。诊断为 BC 且年龄≤50 岁的患者比诊断为 BC 且年龄>50 岁的患者具有更高的 BRCA1/2 突变发生率（21.1%比 6.9%；P=0.003）。在一级、二级或三级亲属中有 PC 的患者中，突变发生率分别为 15.4%、15.3%和 8.6%（P=0.58）。在整个组中，观察到的 BRCA1/2 突变发生率为 14.2%，预期发生率为 11.8%（O：E 比，1.21；P=0.15）。
在 AJ 乳腺癌-胰腺肿瘤家族中，BRCA1 和 BRCA2 突变以几乎相等的分布观察到，表明这两个基因都与 PC 风险相关。在该人群中，FH 的 PC 被发现对突变发生率的影响有限。
