© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 3, 214-221,
February 5, 2003
© 2003 Oxford University Press
ARTICLE |
BRCA2 Germline Mutations in Familial Pancreatic Carcinoma
Affiliations of authors: S. A. Hahn, B. Korte, W. Schmiegel, Department of Internal Medicine, Knappschaftskrankenhaus University of Bochum, Bochum, Germany; B. Greenhalf, J. P. Neoptolemos (Department of Surgery), I. Ellis (Department of Clinical Genetics), University of Liverpool, Liverpool, U.K.; M. Sina-Frey, H. Rieder, H. Rehder (Department of Clinical Genetics), B. Gerdes, M. Rothmund, D. K. Bartsch (Department of Surgery), R. Kress (Institute of Medical Biometry and Epidemiology), Philipps-University Marburg, Marburg, Germany; A. Ziegler, Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany; J. A. Raeburn, Department of Clinical Genetics, City Hospital, Nottingham, U.K.; D. Campra, Department of Surgery, University of Turin, Turin, Italy; R. Grützmann, Department of Surgery, University Hospital Carl-Gustav-Carus, Technical University of Dresden, Dresden, Germany.
Correspondence to: Detlef K. Bartsch, M.D., Department of Surgery, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany (e-mail: bartsch{at}mailer.uni-marburg.de).
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. E Brand, M. M Lerch, W. S Rubinstein, J. P Neoptolemos, D. C Whitcomb, R. H Hruban, T. A Brentnall, H. T Lynch, M. I Canto, and Participants of the Fourth International Symposium Advances in counselling and surveillance of patients at risk for pancreatic cancer Gut, October 1, 2007; 56(10): 1460 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ghaneh, E. Costello, and J. P Neoptolemos Biology and management of pancreatic cancer Gut, August 1, 2007; 56(8): 1134 - 1152. [Full Text] [PDF]
|
|
|
|
|
|
J. B Greer and D. C Whitcomb Role of BRCA1 and BRCA2 mutations in pancreatic cancer Gut, May 1, 2007; 56(5): 601 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang, S. Chen, K. A. Brune, R. H. Hruban, G. Parmigiani, and A. P. Klein PancPRO: Risk Assessment for Individuals With a Family History of Pancreatic Cancer J. Clin. Oncol., April 10, 2007; 25(11): 1417 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Couch, M. R. Johnson, K. G. Rabe, K. Brune, M. de Andrade, M. Goggins, H. Rothenmund, S. Gallinger, A. Klein, G. M. Petersen, et al. The Prevalence of BRCA2 Mutations in Familial Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 342 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gallmeier and S. E. Kern Targeting Fanconi Anemia/BRCA2 Pathway Defects in Cancer: The Significance of Preclinical Pharmacogenomic Models Clin. Cancer Res., January 1, 2007; 13(1): 4 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Earl, L. Yan, L. J. Vitone, J. Risk, S. J. Kemp, C. McFaul, J. P. Neoptolemos, W. Greenhalf, for the European Registry of Hereditary Pancreatit, R. Kress, et al. Evaluation of the 4q32-34 locus in European familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1948 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Kennedy and A. D. D'Andrea DNA Repair Pathways in Clinical Practice: Lessons From Pediatric Cancer Susceptibility Syndromes J. Clin. Oncol., August 10, 2006; 24(23): 3799 - 3808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Wiktor-Brown, C. A. Hendricks, W. Olipitz, and B. P. Engelward Age-dependent accumulation of recombinant cells in the mouse pancreas revealed by in situ fluorescence imaging PNAS, August 8, 2006; 103(32): 11862 - 11867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Petersen, M. de Andrade, M. Goggins, R. H. Hruban, M. Bondy, J. F. Korczak, S. Gallinger, H. T. Lynch, S. Syngal, K. G. Rabe, et al. Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 704 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jimeno and M. Hidalgo Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol. Cancer Ther., April 1, 2006; 5(4): 787 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M M Lerch Anticipating disaster: the genetics of familial pancreatic cancer Gut, February 1, 2006; 55(2): 150 - 151. [Full Text] [PDF]
|
|
|
|
|
|
C D McFaul, W Greenhalf, J Earl, N Howes, J P Neoptolemos, for the European Registry of Hereditary Pancreatit, R Kress, M Sina-Frey, H Rieder, S Hahn, et al. Anticipation in familial pancreatic cancer Gut, February 1, 2006; 55(2): 252 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Barcenas, G.M. M. Hosain, B. Arun, J. Zong, X. Zhou, J. Chen, J. M. Cortada, G. B. Mills, G. E. Tomlinson, A. R. Miller, et al. Assessing BRCA Carrier Probabilities in Extended Families J. Clin. Oncol., January 20, 2006; 24(3): 354 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsubayashi, M. Canto, N. Sato, A. Klein, T. Abe, K. Yamashita, C. J. Yeo, A. Kalloo, R. Hruban, and M. Goggins DNA Methylation Alterations in the Pancreatic Juice of Patients with Suspected Pancreatic Disease Cancer Res., January 15, 2006; 66(2): 1208 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Kennedy and A. D. D'Andrea The Fanconi Anemia/BRCA pathway: new faces in the crowd Genes & Dev., December 15, 2005; 19(24): 2925 - 2940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C J van Asperen, R M Brohet, E J Meijers-Heijboer, N Hoogerbrugge, S Verhoef, H F A Vasen, M G E M Ausems, F H Menko, E B Gomez Garcia, J G M Klijn, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary J. Med. Genet., September 1, 2005; 42(9): 711 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goggins Molecular Markers of Early Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4524 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Pancreatic Section Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas Gut, June 1, 2005; 54(suppl_5): v1 - v16. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Couch, M. R. Johnson, K. Rabe, L. Boardman, R. McWilliams, M. de Andrade, and G. Petersen Germ Line Fanconi Anemia Complementation Group C Mutations and Pancreatic Cancer Cancer Res., January 15, 2005; 65(2): 383 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Garber and K. Offit Hereditary Cancer Predisposition Syndromes J. Clin. Oncol., January 10, 2005; 23(2): 276 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Whitcomb Inflammation and Cancer V. Chronic pancreatitis and pancreatic cancer Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G315 - G319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Van der Heijden, J. R. Brody, E. Gallmeier, S. C. Cunningham, D. A. Dezentje, D. Shen, R. H. Hruban, and S. E. Kern Functional Defects in the Fanconi Anemia Pathway in Pancreatic Cancer Cells Am. J. Pathol., August 1, 2004; 165(2): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beger, M. Ramadani, S. Meyer, G. Leder, M. Kruger, K. Welte, F. Gansauge, and H. G. Beger Down-Regulation of BRCA1 in Chronic Pancreatitis and Sporadic Pancreatic Adenocarcinoma Clin. Cancer Res., June 1, 2004; 10(11): 3780 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Liede, B. Y. Karlan, and S. A. Narod Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature J. Clin. Oncol., February 15, 2004; 22(4): 735 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. van der Heijden, R. H. Hruban, and S. E. Kern Reply Cancer Res., October 15, 2003; 63(20): 6999 - 7001. [Full Text] [PDF]
|
|
|
|
|
|
M. S. van der Heijden, C. J. Yeo, R. H. Hruban, and S. E. Kern Fanconi Anemia Gene Mutations in Young-onset Pancreatic Cancer Cancer Res., May 15, 2003; 63(10): 2585 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Petersen and R. H. Hruban Familial Pancreatic Cancer: Where Are We in 2003? J Natl Cancer Inst, February 5, 2003; 95(3): 180 - 181. [Full Text] [PDF]
|
|