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.

Public Health Relevance

Pancreatic cancer is the deadliest of the common cancers and one of commonest causes of cancer death. Detecting pancreatic cancer at an early stage greatly improves survival from pancreatic cancer. We propose to validate the diagnostic accuracy of a tumor marker gene blood test for pancreatic cancer early detection and use this test in a clinical trial to improve the early detection of pancreatic cancer for patients with an increased susceptibility to pancreatic cancer undergoing pancreatic screening.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA176828-06A1
Application #
10051443
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Rinaudo, Jo Ann S
Project Start
2013-07-01
Project End
2025-06-30
Budget Start
2020-07-15
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Raman, Aadhithya; Lennon, Anne Marie (2018) Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas. Visc Med 34:178-181
Poruk, Katherine E; Griffin, James; Makary, Martin A et al. (2018) Blood Type as a Predictor of High-Grade Dysplasia and Associated Malignancy in Patients with Intraductal Papillary Mucinous Neoplasms. J Gastrointest Surg :
Canto, Marcia Irene; Almario, Jose Alejandro; Schulick, Richard D et al. (2018) Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology 155:740-751.e2
Robinson, Cemre; Estrada, Andrea; Zaheer, Atif et al. (2018) Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome. J Clin Endocrinol Metab 103:4293-4303
Hata, Tatsuo; Suenaga, Masaya; Marchionni, Luigi et al. (2018) Genome-Wide Somatic Copy Number Alterations and Mutations in High-Grade Pancreatic Intraepithelial Neoplasia. Am J Pathol 188:1723-1733
Tamura, Koji; Yu, Jun; Hata, Tatsuo et al. (2018) Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer. Proc Natl Acad Sci U S A 115:4767-4772
Ayars, Michael; O'Sullivan, Eileen; Macgregor-Das, Anne et al. (2017) IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth. Oncotarget 8:83370-83383
Suenaga, Masaya; Sadakari, Yoshihiko; Almario, Jose Alejandro et al. (2017) Using an endoscopic distal cap to collect pancreatic fluid from the ampulla (with video). Gastrointest Endosc 86:1152-1156.e2
Pea, Antonio; Yu, Jun; Rezaee, Neda et al. (2017) Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas. Ann Surg 266:133-141
Shindo, Koji; Yu, Jun; Suenaga, Masaya et al. (2017) Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma. J Clin Oncol 35:3382-3390

Showing the most recent 10 out of 25 publications