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Brief Communication
Linkage Analysis of Chromosome 4 in Families with Familial Pancreatic Cancer
Alison P. Klein, Mariza de Andrade, Ralph H. Hruban, Melissa Bondy, Ann G. Schwartz, Steven Gallinger, Henry T. Lynch, Sapna Syngal, Kari G. Rabe, Michael G. Goggins and Gloria M. Petersen
volume 6 | issue 3
March 2007Pages: 320 - 323
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BACKGROUND: Approximately 10% of pancreatic ductal adenocarcinomas have a familial basis. While a small portion of this familial clustering can be explained by inherited mutations in known genes (BRCA2, p16/CDKN2A, PRSS1, and STK11), the genetic basis for the majority of this familial clustering remains unknown. In addition, a pancreatic cancer susceptibility locus has been reported to be linked to chromosome 4q32-34 in a single family having a high penetrance of early-onset pancreatic ductal adenocarcinoma and pancreatic insufficiency. The goal of this study is to determine if linkage to chromosome 4q exists in our series of well-characterized families with idiopathic familial pancreatic cancer enrolled in the Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE).
METHODS: Parametric and non-parametric linkage analyses were performed using 21 microsatellite markers on chromosome 4 on affected individuals with pancreatic cancer from 42 familial pancreatic cancer kindreds.
RESULTS: Markov Chain Monte Carlo parametric and non-parametric linkage analyses using SIMWALK2 as well as non-parametric linkage analysis using MERLIN did not provide strong evidence of linkage in this region (LOD<1.0). Only one family provided a multipoint LOD score of >0.5 adjacent to the reported region.
CONCLUSIONS: Our results do not support linkage to the 4q32-34 region in the majority of our familial pancreatic cancer kindreds. However, because multiple pancreatic cancer susceptibility genes are likely to exist, it is possible that a subset of the families in this study may be linked to this region.
Authors
Alison P. Klein
Johns Hopkins University, Baltimore, Maryland
Mariza de Andrade
Mayo Clinic College of Medicine, Rochester, Minnesota
Ralph H. Hruban
Johns Hopkins University School of Medicine, Baltimore, MD
Melissa Bondy
M.D. Anderson Cancer Center, Houston, Texas
Ann G. Schwartz
Karmanos Cancer Institute at Wayne State University, Detroit, Michigan
Steven Gallinger
Mt. Sinai Hospital, Toronto, Canada
Henry T. Lynch
Creighton University, Omaha, Nebraska
Sapna Syngal
Dana-Farber Cancer Institute, Boston, Massachusetts
Kari G. Rabe
Mayo Clinic College of Medicine, Rochester, MN
Michael G. Goggins
Johns Hopkins University School of Medicine, Baltimore, MD
Gloria M. Petersen
Mayo Clinic College of Medicine, Rochester, MN
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.