Skip Navigation



Carcinogenesis Advance Access published online on April 9, 2007
Carcinogenesis, doi:10.1093/carcin/bgm077
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/9/1914    most recent
bgm077v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Shanmugam, K. S.
Right arrow Articles by Burwinkel, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shanmugam, K. S.
Right arrow Articles by Burwinkel, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The functional genetic variant Arg324Gly of frizzled-related protein (FRZB) is associated with colorectal cancer risk

Kalai Selvi Shanmugam1,2,*, Hermann Brenner3, Michael Hoffmeister3, Jenny Chang-Claude4 and Barbara Burwinkel1,2

1 Helmholtz-University Group Molecular Epidemiology, German Cancer Research Center, Heidelberg, Germany
2 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
3 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
4 Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany

* Corresponding author: Kalai Selvi Shanmugam, German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. E-mail: k.shanmugam{at}dkfz.de, Tel.: +49-6221-421811, Fax: +49-6221-421810

The Wnt/ß-catenin pathway plays a central role in colorectal tumorigenesis. Frizzled-related protein (FRZB, also termed secreted frizzled-related protein 3, sFRP3) antagonizes the signaling of wingless (Wnt) ligands through the frizzled membrane-bound receptors, resulting in ß-catenin destabilization thereby suppressing the expression of target genes. Recently, the FRZB Gly324 variant has been shown to have an attenuated ability to antagonize Wnt signaling and to be associated with an increased osteoarthritis risk. Here, we investigated, for the first time, the role of Arg324Gly (970C>G) along with Arg200Trp (598C>T) on colorectal cancer (CRC) risk by analyzing 659 patients and 607 control individuals drawn from the German DACHS (Darmkrebs: Chancen der Verhütung durch Screening) study. While Arg200Trp showed no effect on CRC risk, we found homozygous carriers of Gly324 more frequent in cases than in controls, leading to a significantly increased risk for CRC (OR = 5.1, 95% CI = 1.74-14.71, P < 0.001). The association was stronger in rectal cancer (OR = 7.52, 95% CI = 2.40-23.25, P < 0.0001) than in colon cancer (OR = 3.66, 95% CI = 1.14-11.76, P < 0.05). Since modified Wnt signaling and down-regulation of frizzled-related proteins have been observed in many human cancers, this variant may also affect the susceptibility to other cancers.

Key Words: colorectal cancer • secreted frizzled-related protein 3 • polymorphism • Wnt/ß-catenin • genetic risk factor

Received January 29, 2007; revised March 23, 2007; accepted March 28, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.