Petersen Gloria M, de Andrade Mariza, Goggins Michael, Hruban Ralph H, Bondy Melissa, Korczak Jeannette F, Gallinger Steven, Lynch Henry T, Syngal Sapna, Rabe Kari G, Seminara Daniela, Klein Alison P
Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):704-10. doi: 10.1158/1055-9965.EPI-05-0734.
We have organized the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium to identify susceptibility genes in familial pancreatic cancer (FPC). The Consortium comprises seven data collection centers, a statistical genetics core, and a pathology/archival genotyping core. We recruit kindreds containing two or more affected blood relatives ascertained through incident pancreatic adenocarcinoma cases, physician referrals, and/or through Internet recruitment. Accrual to a database containing core clinical, demographic, lifestyle, and family history information from questionnaires is ongoing, along with biospecimen collection. To date, 13,147 patients have been screened for family history, of whom 476 (50% male) probands and 1,912 of their adult (99% unaffected) relatives have been enrolled. Of these, 379 kindreds meet criteria for FPC, having at least two first-degree relatives with pancreatic cancer. Cumulative incidence curves using available age of diagnosis (onset) among and affected relatives were compared with those for incident pancreatic cancer cases reported to 13 U.S. Surveillance Epidemiology and End Results (SEER) sites from 1973 to 2000 (N = 72,700). The mean age +/- SD at diagnosis among 466 PACGENE probands and 670 affected relatives was 64.1 +/- 11.8 and was 65.4 +/- 11.6 for the subset of 369 FPC probands and 429 relatives. Both samples were significantly younger than the mean age at diagnosis in the SEER population (70.0 +/- 12.1 years; differences in curves versus SEER, P < 0.001). Age at diagnosis (excluding probands) in FPC kindreds does not decrease with increasing number of affected individuals. In our sample, younger age at diagnosis was observed whether we grouped probands by recruitment sites that predominantly recruited through high-risk referrals, or through screening all pancreatic cancer patients for family history. Linkage studies are ongoing. The PACGENE Consortium will be a valuable family-based resource that will greatly enhance genetic epidemiology research in pancreatic cancer.
我们组建了胰腺癌遗传流行病学（PACGENE）联盟，以确定家族性胰腺癌（FPC）中的易感基因。该联盟由七个数据收集中心、一个统计遗传学核心以及一个病理学/档案基因分型核心组成。我们通过新发胰腺腺癌病例、医生转诊和/或网络招募，招募包含两个或更多受影响血亲的家族。目前正在将通过问卷调查获得的核心临床、人口统计学、生活方式和家族史信息录入数据库，并进行生物样本采集。迄今为止，已对13147名患者进行了家族史筛查，其中476名（50%为男性）先证者及其1912名成年（99%未受影响）亲属已被纳入。其中，379个家族符合FPC标准，即至少有两名一级亲属患有胰腺癌。将受影响亲属中可用的诊断（发病）年龄的累积发病率曲线与1973年至2000年报告给美国13个监测、流行病学和最终结果（SEER）站点的新发胰腺癌病例的曲线进行了比较（N = 72700）。466名PACGENE先证者和670名受影响亲属的诊断平均年龄±标准差为64.1±11.8岁，369名FPC先证者和429名亲属的子集的诊断平均年龄±标准差为65.4±11.6岁。这两个样本的诊断平均年龄均显著低于SEER人群（70.0±12.1岁；与SEER的曲线差异，P < 0.001）。FPC家族中诊断时的年龄（不包括先证者）不会随着受影响个体数量的增加而降低。在我们的样本中，无论我们是根据主要通过高风险转诊招募的先证者分组，还是通过对所有胰腺癌患者进行家族史筛查来分组，都观察到了诊断时较年轻的年龄。连锁研究正在进行中。PACGENE联盟将成为一个宝贵的基于家族的资源，将极大地加强胰腺癌的遗传流行病学研究。
