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

The Wnt–β-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 β-catenin destabilizatio...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2007-09, Vol.28 (9), p.1914-1917
Main Authors: Shanmugam, Kalai S., Brenner, Hermann, Hoffmeister, Michael, Chang-Claude, Jenny, Burwinkel, Barbara
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Arginine
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Case-Control Studies
Colorectal cancer
Colorectal Neoplasms - epidemiology
Colorectal Neoplasms - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Genetic Linkage
Genetic Variation
Glycine
Glycoproteins - genetics
Humans
Medical sciences
Risk
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary:The Wnt–β-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 β-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. Although 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 [odds ratio (OR) = 5.1, 95% confidence interval (95% CI) = 1.74–14.71, P 
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgm077