Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma

Holter, Spring; Borgida, Ayelet; Dodd, Anna; Grant, Robert; Semotiuk, Kara; Hedley, David; Dhani, Neesha; Narod, Steven; Akbari, Mohammad; Moore, Malcolm; Gallinger, Steven

doi:10.1200/jco.2014.59.7401

Cited by 401BRCA gene mutations in cancerPancreatic and Hepatic Oncology ResearchGenetic factors in colorectal cancer

Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma

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Holter, Spring, Borgida, Ayelet, Dodd, Anna, Grant, Robert, Semotiuk, Kara, Hedley, David, Dhani, Neesha, Narod, Steven +3 more·2015·Journal of Clinical Oncology

DOI 10.1200/jco.2014.59.7401

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Abstract

Purpose: The main purpose of this study was to determine the prevalence of pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based cohort of patients with pancreatic ductal adenocarcinoma and describe the clinical and family history characteristics. Patients and Methods: Unselected, consecutive, incident patients with pancreatic ductal adenocarcinoma were recruited at a single cancer center over a 2-year period. Participants provided blood for DNA analysis and cancer family history, and cancer treatment records were reviewed. DNA from all patients was analyzed by Sanger sequencing and multiplex ligation-dependent probe amplification for germline variants in BRCA1 and BRCA2. Results: Three hundred six patients were eligible for analysis. Pathogenic germline BRCA mutations were identified in 14 patients (4.6%; 95% CI, 2.2% to 6.9%), including 11 patients with a BRCA2 mutation and three patients with a BRCA1 mutation. Having a cancer family history that met genetic testing criteria of the National Comprehensive Cancer Network or the Ontario Ministry of Health and Long-Term Care or self-reporting as Ashkenazi Jewish was significantly associated with BRCA mutation carrier status (P = .02, P < .001, and P = .05, respectively). However, the majority of the BRCA mutation–positive patients did not actually meet these genetic testing criteria. Conclusion: Pathogenic BRCA mutations were identified in 4.6% of a large cohort of clinic-based patients. Considering the implications for family members of BRCA carriers, and possibly tailored chemotherapeutic treatment of patients, our finding has implications for broader BRCA genetic testing for patients with pancreatic ductal adenocarcinoma.

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Genomic risk contributes to up to 8% of PDAC cases.
“Recent studies estimate that genomic risk contributes to up to 8% of PDAC cases,180–184”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [184]
Classic medical history features (young age at PDAC diagnosis and family history of pancreatic or other cancers) have poor sensitivity in identifying individuals at high genomic risk for pancreatic cancer.
“However, these classic features have poor sensitivity in identifying individuals at high genomic risk for pancreatic cancer.182–185”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [184]

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Abstract 12: Germline BRCA mutations in an unselected cohort of patients with pancreatic adenocarcinoma
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Self-citation
Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
Lee, K., Yoo, C., Kim, K., Park, K., Chang, H.-M., Kim, T. W., Lee, J., Lee, W., Lee, S. S., Park, D. H., et al. (2017) · Investigational New Drugs · doi:10.1007/s10637-017-0497-1 · Cited by 15 · see citing works
BRCA1 and BRCA2 Germline Mutations Are Frequently Demonstrated in a Pancreatic Ductal Adenocarcinoma Cohort Referred For Genetic Testing
Frado, L. E., Hwang, C., Kumar, S., Khanna, L. G., Levinson, E., Chung, W. K., Chabot, J. A., HAROLD, F. H., & Lucas, A. L. (2013) · The American Journal of Gastroenterology · doi:10.14309/00000434-201310001-00268
Identification of germline genetic mutations in patients with pancreatic adenocarcinoma.
Salo‐Mullen, E. E., O'Reilly, E. M., Kelsen, D. P., Lowery, M. A., Yu, K. H., Rau‐Murthy, R., Siegel, B., Saltz, L. B., Kurtz, R. C., Offit, K., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.4_suppl.159 · Cited by 2 · see citing works
Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history
Chaffee, K. G., Oberg, A. L., McWilliams, R. R., Majithia, N., Allen, B. A., Kidd, J., Singh, N., Hartman, A.-R., Wenstrup, R. J., & Petersen, G. M. (2018) · Genetics in Medicine · doi:10.1038/gim.2017.85 · Cited by 144 · see citing works

Authors: Holter, S., Borgida, A., Dodd, A., Grant, R., Semotiuk, K., Hedley, D., Dhani, N., Narod, S., Akbari, M., Moore, M., & Gallinger, S.
Affiliations: Mount Sinai Hospital (CA)
Spring Holter, Ayelet Borgida, Robert Grant, Kara Semotiuk, and Steven Gallinger, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital; Anna Dodd, David Hedley, Neesha Dhani, Malcolm Moore, and Steven Gallinger, McCain Pancreatic Cancer Centre, University Health Network; and Steven Narod and Mohammad Akbari, Women's College Research Institute, Toronto, Ontario, Canada.
ORCID: Borgida, Ayelet
Dodd, Anna
Grant, Robert
Semotiuk, Kara
Hedley, David
Dhani, Neesha
Narod, Steven
Akbari, Mohammad
Moore, Malcolm
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2015-10-01
Volume: 33
Issue: 28
Pages: 3124-3129
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2014.59.7401
OpenAlex: W2161479848
Cited by: 398
References: 39
Citations by year: 2026: 18 · 2025: 19 · 2024: 23 · 2023: 40 · 2022: 40 · 2021: 71 · 2020: 50 · 2019: 27 · 2018: 42 · 2017: 30 · 2016: 26 · 2015: 12
FWCI: 25.18
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Cancer Society Research Institute
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: germline BRCA1 mutation, germline BRCA2 mutation, pancreatic ductal adenocarcinoma, family history of cancer, Ashkenazi Jewish ancestry, hereditary cancer predisposition
MeSH terms: Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Gene Frequency, Humans, Jews, Male, Middle Aged, Ontario, Pancreatic Neoplasms, Pedigree, Phenotype, Prognosis, Prospective Studies, Risk Factors, Incidence, Germ-Line Mutation, BRCA1 Protein, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, BRCA2 Protein, Heredity, Multiplex Polymerase Chain Reaction

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Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma

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