Linkage analysis of chromosome 4 in families with familial pancreatic cancer

Cancer Biol Ther. 2007 Mar;6(3):320-3. doi: 10.4161/cbt.6.3.3721. Epub 2007 Mar 15.


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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Pancreatic Ductal / genetics*
  • Chromosomes, Human, Pair 4 / genetics*
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Humans
  • Lod Score*
  • Male
  • Markov Chains
  • Middle Aged
  • Monte Carlo Method
  • Pancreatic Neoplasms / genetics*
  • Pedigree