Pancreatic Cancer Genetics
The aim of this study is to determine the frequency of the three most common BRCA1 and BRCA2 genetic mutations that are commonly found in Ashkenazi Jewish patients with pancreatic cancer. Testing for BRCA1 and BRCA2 mutations in relatives of hereditary pancreatic cancer patients may have a significant impact; allowing for early screening, treatment, and resection of pre-malignant tissue or malignant lesions.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Molecular Genetics and Epidemiology of Pancreatic Cancer in Ashkenazi Jewish Patients|
- Frequency of Three BRCA1/2 Mutations in Ashkenazi Jewish Patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]The primary aim of this study is to determine the combined frequency of BRCA1 (185delAG, 5382insC) and BRCA2(6174delT) mutations in Ashkenazi Jewish pancreatic cancer patients.
- Individual Frequency of Three Mutations [ Time Frame: 1 year ] [ Designated as safety issue: No ]Individual frequency of these mutations three mutations BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) mutations.
- Frequency of disease modifying mutations [ Time Frame: 1 year ] [ Designated as safety issue: No ]Determine the frequency of disease modifying mutations such as MSH2 A636P, APC I1307K, P53, R72P, CHEK2 S428F, RAD51 G135C and MTHFR V222A.
- Other Variables in Patients with Positive Mutations [ Time Frame: 1 year ] [ Designated as safety issue: No ]Study death from any cause, disease-free survival, stage of disease at time of presentation (Pan-In Stage 1-3 and tumor stages), differences in tissue pathology, risk factors, treatment decisions, and development of another malignancy in patients with positive mutations.
Biospecimen Retention: Samples With DNA
- Peripheral Blood Specimens: Three tubes of blood will be collected from each study participant. Two tubes will be EDTA-whole blood and one tube will be serum. Each tube will contain ~4-5 ml. A portion of the blood will be utilized to extract white blood cells that will be immortalized by EBV infection.
- Archived Fixed Tissue Samples: Tissue blocks from surgery performed at CUMC or elsewhere, will be requested after obtaining consent for study participation.
- Fresh Tissue Collection: At the time of surgery for tumor resection, tumor and adjacent normal tissue will be requested from the Pathology Department. At the time of endoscopy, aspirated fluid or biopsied tissue will be requested. No additional tissue will be resected beyond that required for surgical or endoscopic management.
- Genetic Testing: All genetic testing will be performed in a research laboratory. Test results from research laboratories will not be disclosed to patients.
|Study Start Date:||May 2007|
|Estimated Study Completion Date:||August 2012|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Pancreatic cancer is the fourth leading cause of death from malignancy in the United States. Up to 15% of pancreatic cancers have a hereditary component. Several gene mutations and cancer syndromes have been identified that are frequently found in greater frequency in individuals with pancreatic cancer, including the breast ovary cancer syndrome (BRCA1/BRCA2 mutations). No studies adequately describe the epidemiology of inherited pancreatic cancer and genetic risk factors that may modify the penetrance of BRCA1/BRCA2 mutations. The primary aim of this study is to determine the frequency of BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) mutations in Ashkenazi Jewish pancreatic cancer patients. Secondary endpoints will include determining the individual frequency of these mutations and other disease-modifying mutations, death from any cause, disease-free survival, and stage of disease at time of presentation, differences in tissue pathology, risk factors, treatment decisions and development of metachronous malignancies. We plan to study 385 patients, which will enable the true frequency of the mutation to be estimated. Although the impact of BRCA1/BRCA2 mutations will be initially studied in the Ashkenazi population, these data will be widely applicable to other pancreatic cancer patients carrying BRCA1/BRCA2 mutations. Testing for BRCA1 and BRCA2 mutations in relatives of hereditary pancreatic cancer patients may allow early screening, treatment, and resection of pre-malignant tissue or malignant lesions.
|Contact: Wendy K Chung, MDemail@example.com|
|Contact: Ashley Dikosfirstname.lastname@example.org|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Wendy K Chung, MD email@example.com|
|Contact: Ashley Dikos firstname.lastname@example.org|
|Principal Investigator: Wendy K Chung, MD|
|Principal Investigator:||Wendy K Chung, MD||Columbia University|