title: Linkage analysis of chromosome 4 in families with familial pancreatic cancer.
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.
authors.affiliation: The Sol Goldman Pancreatic Research Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231, USA. aklein1@jhmi.edu
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
authors.forename: Kari G
authors.initials: KG
authors.lastname: Rabe
authors.forename: Michael G
authors.initials: MG
authors.lastname: Goggins
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
mesh_terms: D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009010:Monte Carlo Method; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree