Using Markers to Improve Pancreatic Cancer Screening

大多数胰腺癌患者都有晚期不治之症，但 被诊断为I期胰腺癌的患者预后要好得多。早期发现 胰腺癌需要简单有效的可应用的胰腺筛查试验 高危人群。胰腺癌筛查(CAPS)研究目前如下 约1000名家族性/遗传性“高危”患者接受定期的胰腺监测。 CAPS计划的最新结果表明，在 胰腺监测被淡化；保持年度监测的人中有40% 一期胰腺癌。这些结果表明，及早发现可以改善整体情况 胰腺癌患者的预后。循环中的肿瘤标志物检测目前还没有 用于胰腺监测。已知遗传因素会影响肿瘤标记物水平，但 基因测试还没有得到评估，以确定它们是否可以提高肿瘤的准确性 记号笔。最近来自PI实验室的研究表明，正常的参考范围 常用的肿瘤标志物(CA19-9、CA-125和CEA)更好地由个人的 肿瘤标志物基因分型。肿瘤标志物基因分型检测可提高诊断敏感性 与传统的诊断界值相比，肿瘤标志物的特异度为99%。我们建议 建立基因定义的肿瘤标记物水平正常参考范围，并评估其 对接受胰腺成像的患者进行前瞻性临床试验的诊断准确性 通过我们的CAPS计划进行监视。每年一次的胰腺血检 监测有望提高对早期胰腺癌的发现。

Most patients with pancreatic cancer present with advanced incurable disease, but patients diagnosed with Stage I pancreatic cancer have a much better outcome. The early detection of pancreatic cancer requires simple and effective pancreatic screening tests that can be applied to high risk populations. The Cancer of the Pancreas Screening (CAPS) study currently follows a familial/genetic “high-risk” cohort of ~1000 patients undergo regular pancreatic surveillance. Recent results from the CAPS program indicate that pancreatic cancers detected during pancreatic surveillance are down-staged; 40% of those who maintained annual surveillance had a Stage I pancreatic cancer. These results indicate that early detection can improve overall outcome of patients with pancreatic cancer. Circulating tumor marker tests are not currently used for pancreas surveillance. Genetic factors are known to influence tumor marker levels, but gene tests have not been evaluated to determine if they could improve the accuracy of tumor markers. Recent studies from the PI's lab indicate that the normal reference ranges of commonly used tumor markers (CA19-9, CA-125 and CEA) are better defined by an individual's tumor marker genotype. A tumor marker genotype test can improve the diagnostic sensitivity of tumor markers at 99% specificity compared to conventional diagnostic cut-offs. We propose to establish genetically-defined normal reference ranges for tumor marker levels and evaluate their diagnostic accuracy in a prospective clinical trial of patients undergoing pancreatic imaging surveillance through our CAPS program. The addition of annual blood tests to pancreatic surveillance is expected to improve the detection of early-stage pancreatic cancer.