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BRCA2 Germline Mutations in Familial Pancreatic Carcinoma
Abstract
BACKGROUND: Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer. METHODS: We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2. RESULTS: Three (12%, exact 95% confidence interval [CI] = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer. CONCLUSIONS: Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.
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Metadata
- Authors
- Hahn, S. A., Greenhalf, B., Ellis, I., Sina-Frey, M., Rieder, H., Korte, B., Gerdes, B., Kress, R., Ziegler, A., Raeburn, J. A., Campra, D., Grutzmann, R., Rehder, H., Rothmund, M., Schmiegel, W., Neoptolemos, J. P., & Bartsch, D. K.
- Affiliations
- Universitätsklinikum Knappschaftskrankenhaus Bochum (DE)
- Corresponding author
- Hahn, S. A.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-05
- Volume
- 95
- Issue
- 3
- Pages
- 214-221
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W1544246953
- Cited by
- 480
- References
- 40
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 11 · 2023: 13 · 2022: 21 · 2021: 19 · 2020: 11 · 2019: 14 · 2018: 16 · 2017: 21 · 2016: 33 · 2015: 24 · 2014: 23 · 2013: 25 · 2012: 35
- FWCI
- 13.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- 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
- BRCA2, germline mutations, familial pancreatic cancer, pancreatic ductal adenocarcinoma, frameshift mutation, unclassified variants, hereditary cancer predisposition, molecular genetic testing, genetic counseling, European family
- MeSH terms
- Adult, Aged, DNA, Neoplasm, Europe, Female, Germany, Humans, Lymphocytes, Male, Middle Aged, Pancreatic Neoplasms, Pedigree, Phenotype, Registries, Frameshift Mutation, Sequence Analysis, DNA, Germ-Line Mutation, Genetic Predisposition to Disease, Genes, BRCA2
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