BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts

Lucas, Aimee L.; Frado, Laura E.; Hwang, Caroline; Kumar, Sheila; Khanna, Lauren G.; Levinson, Elana J.; Chabot, John A.; Chung, Wendy K.; Frucht, Harold

doi:10.1002/cncr.28662

Cited by 68BRCA gene mutations in cancerPancreatic and Hepatic Oncology ResearchGenetic factors in colorectal cancer

BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts

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Lucas, Aimee L., Frado, Laura E., Hwang, Caroline, Kumar, Sheila, Khanna, Lauren G., Levinson, Elana J., Chabot, John A., Chung, Wendy K. +1 more·2014·Cancer

DOI 10.1002/cncr.28662PMC PMC5494829

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Abstract

BACKGROUND: Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) is due to a genetic predisposition, including the breast and ovarian cancer syndrome germline mutations BRCA1 and BRCA2. Knowledge of specific genetic mutations predisposing to PDAC may enable risk stratification, early detection, and the development of effective screening and surveillance programs. In the current study, the authors attempted to determine the diagnostic yield of testing for BRCA1/2 germline mutations in a PDAC screening cohort and a PDAC cohort referred for genetic testing. METHODS: Patients in a high‐risk PDAC prevention and genetics program or those with a personal history of PDAC who were referred for genetic evaluation underwent testing for BRCA1/2 germline mutations. Clinical BRCA1/2 genetic testing included testing for the 3 Ashkenazi Jewish founder mutations or BRCA1/2 comprehensive testing. RESULTS: A total of 37 patients without PDAC underwent BRCA1/2 testing at the study institution. Genetic testing identified 7 patients who were BRCA1/2 carriers for a yield of 18.9%. Six patients carried Ashkenazi Jewish founder mutations (3 with BRCA1 and 3 with BRCA2), and 1 patient was found to have a BRCA2 mutation on comprehensive testing. Thirty‐two patients with PDAC underwent BRCA1/2 genetic testing. Five patients had Ashkenazi Jewish founder mutations (2 with BRCA1 and 3 with BRCA2), and 2 patients were found to have BRCA2 mutations on comprehensive testing. The diagnostic yield was 7 of 32 patients (21.9%). CONCLUSIONS: BRCA1/2 testing is useful in PDAC risk stratification and alters risk assignment and screening recommendations for mutation‐positive patients and their families. Clinical BRCA1/2 testing should be considered in patients of Ashkenazi Jewish descent with a personal history or family history of PDAC, even in the absence of a family history of breast and ovarian cancer. Cancer 2014;120:1960–1967. © 2014 American Cancer Society.

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These deleterious variants also confer risk for other cancers.
“These variants also confer risk for other cancers.”
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Authors: Lucas, A. L., Frado, L. E., Hwang, C., Kumar, S., Khanna, L. G., Levinson, E. J., Chabot, J. A., Chung, W. K., & Frucht, H.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Columbia University Irving Medical Center (US)
University of Southern California (US)
Stanford University (US)
Corresponding author: Lucas, Aimee L.
ORCID: Lucas, Aimee L.
Kumar, Sheila
Khanna, Lauren G.
Chung, Wendy K.
Venue: Cancer
Publisher: Wiley
Published: 2014-04-15
Volume: 120
Issue: 13
Pages: 1960-1967
ISSN: 0008-543X (ISSN-L)
1097-0142
DOI: 10.1002/cncr.28662
PMC: PMC5494829
OpenAlex: W1488988442
Cited by: 68
References: 27
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 1
FWCI: 4.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Cancer (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK083256)
Hirshberg Foundation for Pancreatic Cancer Research
National Institutes of Health (UL1 TR000040)
American College of Gastroenterology (ACG-CR-070-2012)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: BRCA1, BRCA2, germline mutations, pancreatic ductal adenocarcinoma, pancreatic cancer screening, genetic susceptibility, diagnostic yield, risk stratification, hereditary cancer
MeSH terms: Adult, Aged, Female, Genetic Testing, Humans, Jews, Male, Mass Screening, Middle Aged, Pancreatic Neoplasms, Risk Factors, Cohort Studies, Germ-Line Mutation, Risk Assessment, Founder Effect, BRCA1 Protein, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, BRCA2 Protein, Early Detection of Cancer

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BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high‐risk pancreatic cancer screening and pancreatic cancer cohorts

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