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, Gloria M. Petersen

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 nonparametric 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 nonparametric linkage analyses using SIMWALK2 as well as nonparametric 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.

Original languageEnglish (US)
Pages (from-to)320-323
Number of pages4
JournalCancer Biology and Therapy
Volume6
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Adenocarcinoma
  • Familial pancreatic cancer
  • Gastrointestinal cancer
  • Genetics
  • Hereditary
  • Linkage analysis
  • Pancreatic cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Klein, A. P., De Andrade, M., Hruban, R. H., Bondy, M., Schwartz, A. G., Gallinger, S., Lynch, H. T., Syngal, S., Rabe, K. G., Goggins, M. G., & Petersen, G. M. (2007). Linkage analysis of chromosome 4 in families with familial pancreatic cancer. Cancer Biology and Therapy, 6(3), 320-323. https://doi.org/10.4161/cbt.6.3.3721