Pancreatic Cancer Genetics

Molecular Genetics and Epidemiology of Pancreatic Cancer in Ashkenazi Jewish Patients

The aim of this study is to determine the frequency of the three most common BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (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 Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer

Detailed Description

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.

The investigator plans to study about 100 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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Fay Kastrinos, MD; Phone Number: 212-305-1021; Email: fk18@columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Fay Kastrinos, MD; Phone Number: 212-305-1021; Email: fk18@columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study subjects will be pancreatic cancer patients at CUMC who are of Ashkenazi Jewish descent.

Description

Inclusion Criteria:

• Patients diagnosed with pancreatic cancer.
• Patients are of Ashkenazi Jewish descent.
• Patients have been Columbia Pancreatic Cancer Prevention Program Registry and Tissue Bank for High-Risk Individuals (IRB-AAAA6154).

Exclusion Criteria:

• Inability to provide informed consent.
• Under the age of 18 years old.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pancreatic cancer and Ashkenazi decent; Patients with pancreatic cancer will be asked to join the study if they identify themselves as being of Ashkenazi descent, as well as patients at a high-risk of pancreas cancer based on family history, and will be followed from the time of diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Three BRCA1/2 Mutations in Ashkenazi Jewish Patients	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual Frequency of Three Mutations	Individual frequency of these mutations three mutations BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT) mutations.	1 year
Frequency of disease modifying mutations	Determine the frequency of disease modifying mutations such as MSH2 A636P, APC I1307K, P53, R72P, CHEK2 S428F, RAD51 G135C and MTHFR V222A.	1 year

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Fay Kastrinos, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: April 12, 2010
• First Submitted That Met QC Criteria: April 12, 2010
• First Posted (ESTIMATE): April 13, 2010

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Hereditary pancreatic cancer; Breast and Ovarian Cancer Syndrome; BRCA1/2; Ashkenazi Jewish patients
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: AAAC6344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO