Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar;6(3):320-3.
doi: 10.4161/cbt.6.3.3721. Epub 2007 Mar 15.

Linkage analysis of chromosome 4 in families with familial pancreatic cancer

Alison P Klein  1 , 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
Affiliations

Linkage analysis of chromosome 4 in families with familial pancreatic cancer

Alison P Klein et al. Cancer Biol Ther. 2007 Mar.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Results of multipoint non-parametric linkage analyses of chromosome 4
See this image and copyright information in PMC

References

    1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics 2006. CA Cancer J Clin. 2006;56:106–30. - PubMed
    1. Lynch HT, Fitzsimmons M, Smyrk TC. Familial pancreatic cancer: Clinicopathological study of 18 nuclear families. Am J Gastroenterol. 1990;85:54–60. - PubMed
    1. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, Yeo CJ, Jackson CE, Lynch HT, Hruban RH, Kern SE. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996;56:5360–4. - PubMed
    1. Hahn SA, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B, Gerdes B, Kress R, Ziegler A, Raeburn JA, Campra D, Grutzmann R, Rehder H, Rothmund M, Schmiegel W, Neoptolemos JP, Bartsch DK. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003;95:214–21. - PubMed
    1. Murphy KM, Brune KA, Griffin C, Sollenberger JE, Petersen GM, Bansal R, Hruban RH, Kern SE. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: Deleterious BRCA2 mutations in 17% Cancer Res. 2002;62:3789–93. - PubMed