Cancer Causes & Control

, Volume 20, Issue 4, pp 487–490

Genetic variants in frizzled-related protein (FRZB) and the risk of colorectal neoplasia

  • Sonja I. Berndt
  • Wen-Yi Huang
  • Meredith Yeager
  • Joel L. Weissfeld
  • Stephen J. Chanock
  • Richard B. Hayes
Brief Report



The Wnt/APC/β-catenin signaling pathway, which includes frizzled-related protein (FRZB), plays a critical role in the development of colorectal cancer, and recent evidence suggests that the functional polymorphism, FRZB Arg324Gly, may be associated with risk for this disease. To determine if this finding could be replicated, we investigated the association between two FRZB polymorphisms (Arg324Gly and Arg200Trp) and the risk of colorectal adenoma and cancer in nested case–control studies.


Participants consisted of 1,709 adenoma cases, 620 cancer cases, and 1,849 controls within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations with colorectal neoplasia.


No association was observed for either polymorphism or any haplotypes with colorectal adenoma or colorectal cancer (p > 0.05 for all).


Our study does not support the previously observed association between the FRZB 324Gly variant and colorectal cancer risk. However, further study of additional genetic variants within this pathway is still warranted, given the important role of the Wnt signaling pathway in colorectal carcinogenesis.


Colorectal adenoma Colorectal cancer Polymorphism Wnt signaling pathway 



Odds ratio

95% CI

95% confidence interval


Single nucleotide polymorphism


Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Supplementary material

10552_2008_9274_MOESM1_ESM.pdf (109 kb)
(PDF 77 kb)


  1. 1.
    Fodde R, Smits R, Clevers H (2001) APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 1:55–67. doi:10.1038/35094067 PubMedCrossRefGoogle Scholar
  2. 2.
    Kinzler KW, Vogelstein B (2002) Colorectal tumors. In: Vogelstein B, Kinzler KW (eds) The genetic basis of human cancer. McGraw-Hill Companies, Inc., New York, pp 583–612Google Scholar
  3. 3.
    Loughlin J, Dowling B, Chapman K et al (2004) Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci U S A 101:9757–9762. doi:10.1073/pnas.0403456101 PubMedCrossRefGoogle Scholar
  4. 4.
    Shanmugam KS, Brenner H, Hoffmeister M, Chang-Claude J, Burwinkel B (2007) The functional genetic variant Arg324Gly of frizzled-related protein is associated with colorectal cancer risk. Carcinogenesis 28:1914–1917. doi:10.1093/carcin/bgm077 PubMedCrossRefGoogle Scholar
  5. 5.
    Prorok PC, Andriole GL, Bresalier RS et al (2000) Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials 21:273S–309S. doi:10.1016/S0197-2456(00)00098-2 PubMedCrossRefGoogle Scholar
  6. 6.
    Schoen RE, Weissfeld JL, Pinsky PF, Riley T (2006) Yield of advanced adenoma and cancer based on polyp size detected at screening flexible sigmoidoscopy. Gastroenterology 131:1683–1689. doi:10.1053/j.gastro.2006.08.025 PubMedCrossRefGoogle Scholar
  7. 7.
    Berndt SI, Potter JD, Hazra A et al (2008) Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. Hum Mol Genet 17:2665–2672. doi:10.1093/hmg/ddn166 PubMedCrossRefGoogle Scholar
  8. 8.
    Packer BR, Yeager M, Staats B et al (2004) SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes. Nucleic Acids Res 32:D528–D532. doi:10.1093/nar/gkh005 PubMedCrossRefGoogle Scholar
  9. 9.
    Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA (2002) Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70:425–434. doi:10.1086/338688 PubMedCrossRefGoogle Scholar

Copyright information

© National Cancer Institute 2008

Authors and Affiliations

  • Sonja I. Berndt
    • 1
  • Wen-Yi Huang
    • 1
  • Meredith Yeager
    • 1
    • 2
  • Joel L. Weissfeld
    • 3
  • Stephen J. Chanock
    • 1
  • Richard B. Hayes
    • 1
  1. 1.Division of Cancer Epidemiology & GeneticsNational Cancer InstituteBethesdaUSA
  2. 2.Advanced Technology Program, SAIC-Frederick, Inc.National Cancer Institute FrederickFrederickUSA
  3. 3.University of PittsburghPittsburghUSA

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