Pancreatic Cancer Genetics

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Molecular Genetics and Epidemiology of Pancreatic Cancer in Ashkenazi Jewish Patients

Conditions
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Pancreatic Cancer

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pancreatic cancer and Ashkenazi decent<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hereditary pancreatic cancer, Breast and Ovarian Cancer Syndrome, BRCA1/2, Ashkenazi Jewish patients