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 Citations (Scopus)

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

Fingerprint

Chromosomes, Human, Pair 4
Pancreatic Neoplasms
Cluster Analysis
Adenocarcinoma
Chromosomes
BRCA2 Gene
p16 Genes
Exocrine Pancreatic Insufficiency
Markov Chains
Molecular Epidemiology
Penetrance
Neoplasm Genes
Microsatellite Repeats
Mutation

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Klein, A. P., De Andrade, M., Hruban, R. H., Bondy, M., Schwartz, A. G., Gallinger, S., ... Petersen, G. M. (2007). Linkage analysis of chromosome 4 in families with familial pancreatic cancer. Cancer Biology and Therapy, 6(3), 320-323.

Linkage analysis of chromosome 4 in families with familial pancreatic cancer. / Klein, Alison P.; De Andrade, Mariza; Hruban, Ralph H.; Bondy, Melissa; Schwartz, Ann G.; Gallinger, Steven; Lynch, Henry T.; Syngal, Sapna; Rabe, Kari G.; Goggins, Michael G.; Petersen, Gloria M.

In: Cancer Biology and Therapy, Vol. 6, No. 3, 03.2007, p. 320-323.

Research output: Contribution to journalArticle

Klein, AP, De Andrade, M, Hruban, RH, Bondy, M, Schwartz, AG, Gallinger, S, Lynch, HT, Syngal, S, Rabe, KG, Goggins, MG & Petersen, GM 2007, 'Linkage analysis of chromosome 4 in families with familial pancreatic cancer', Cancer Biology and Therapy, vol. 6, no. 3, pp. 320-323.
Klein AP, De Andrade M, Hruban RH, Bondy M, Schwartz AG, Gallinger S et al. Linkage analysis of chromosome 4 in families with familial pancreatic cancer. Cancer Biology and Therapy. 2007 Mar;6(3):320-323.
Klein, Alison P. ; De Andrade, Mariza ; Hruban, Ralph H. ; Bondy, Melissa ; Schwartz, Ann G. ; Gallinger, Steven ; Lynch, Henry T. ; Syngal, Sapna ; Rabe, Kari G. ; Goggins, Michael G. ; Petersen, Gloria M. / Linkage analysis of chromosome 4 in families with familial pancreatic cancer. In: Cancer Biology and Therapy. 2007 ; Vol. 6, No. 3. pp. 320-323.
@article{ae29135e99f548c685d87bcd5659c983,
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.",
author = "Klein, {Alison P.} and {De Andrade}, Mariza and Hruban, {Ralph H.} and Melissa Bondy and Schwartz, {Ann G.} and Steven Gallinger and Lynch, {Henry T.} and Sapna Syngal and Rabe, {Kari G.} and Goggins, {Michael G.} and Petersen, {Gloria M.}",
year = "2007",
month = "3",
language = "English",
volume = "6",
pages = "320--323",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "3",

}

TY - JOUR

T1 - Linkage analysis of chromosome 4 in families with familial pancreatic cancer

AU - Klein, Alison P.

AU - De Andrade, Mariza

AU - Hruban, Ralph H.

AU - Bondy, Melissa

AU - Schwartz, Ann G.

AU - Gallinger, Steven

AU - Lynch, Henry T.

AU - Syngal, Sapna

AU - Rabe, Kari G.

AU - Goggins, Michael G.

AU - Petersen, Gloria M.

PY - 2007/3

Y1 - 2007/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548270466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548270466&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 320

EP - 323

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 3

ER -