Format

Send to

Choose Destination
Genet Med. 2015 Jul;17(7):569-77. doi: 10.1038/gim.2014.153. Epub 2014 Nov 20.

BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.

Author information

1
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
2
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
3
Divison of General Surgery, University of Toronto, Toronto, Ontario, Canada.
4
Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
5
Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan, USA.
6
The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
7
Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
8
1] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA [2] Ludwig Center for Cancer Genetics, Johns Hopkins University, Baltimore, Maryland, USA.
9
Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
10
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
11
Myriad Genetic Laboratories, Inc., Salt Lake City, Utah, USA.
12
Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.

Abstract

PURPOSE:

Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.

METHODS:

Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.

RESULTS:

Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.

CONCLUSION:

Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.

PMID:
25356972
PMCID:
PMC4439391
DOI:
10.1038/gim.2014.153
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center