BRCA2 mutations may be associated with some hereditary pancreatic cancers

Mutations in the breast cancer susceptibility gene BRCA2 may be associated with a predisposition to familial (hereditary) pancreatic cancer, a new study suggests. The findings appear in the February 5 issue of the Journal of the National Cancer Institute.

Familial pancreatic cancers account for as many as 10% of all pancreatic cancer cases. Although no specific gene has been definitively linked to familial pancreatic cancer, some studies have suggested that germline mutations in the BRCA2 gene may be associated with a modest increase in risk of pancreatic cancer. Mutations in BRCA2 have also been associated with an increased risk of breast and ovarian cancers. To examine the frequency of germline BRCA2 mutations in cases of familial pancreatic cancer, Stephan A. Hahn, M.D., of the Knappschaftskrankenhaus University of Bochum in Germany, Detlef K. Bartsch, M.D., of the Philipps-University Marburg in Germany, and their colleagues identified 26 European families with at least two first-degree relatives with pancreatic cancer. None of the families had an increased incidence of other hereditary cancer syndromes.

The authors found that three (12%) of the families carried specific frameshift mutations in their BRCA2 gene. These mutations are predicted to result in a nonfunctional BRCA2 protein. In addition, two other families had BRCA2 genes that contained sequence changes, or unclassified variations whose effect on BRCA2 function is not known. In total, 19% of the families studied had either a frameshift mutation or an unclassified variant of BRCA2.

These findings suggest an important role for BRCA2 mutations in a subpopulation of families with familial pancreatic cancer, the authors conclude. They recommend that future genetic testing and counseling of families with at least two first-degree relatives with pancreatic cancer include analyses for BRCA2 mutations.

In an accompanying editorial, Gloria M. Petersen, Ph.D., of the Mayo Clinic in Rochester, Minn., and Ralph H. Hruban, M.D., of the Johns Hopkins Medical Institutions in Baltimore, Md., caution that, until more is known about the implications of genetic testing for BRCA2 mutations (such as how it relates to cancer screening in mutation carriers), such testing should only be carried out in the research setting.

"It will be important to conduct careful studies of larger numbers of asymptomatic gene mutation carriers and at-risk members of [familial pancreatic cancer] kindreds before a comprehensive set of recommendations for genetic testing and management can be widely accepted," they write.

Contact: Dr. Detlef Bartsch, Philipps-University Marburg, 49-6421-286-6745, bartsch@mailer.uni-marburg.de or Dr. Stephan Hahn, Knappschaftskrankenhaus University of Bochum, 49-234-32-29282, Stephan.Hahn@ruhr-uni-bochum.de

Editorial: Mary Lawson, Mayo Clinic, 507-284-5005; fax: 507-284-8713, Lawson.mary18@mayo.edu

Hahn S, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 2003;95:214–21.

Editorial: Petersen G, Hruban R. Familial pancreatic cancer: Where are we in 2003? J Natl Cancer Inst 2003;95:180–1.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.

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