International Journal of Colorectal Disease

, Volume 23, Issue 2, pp 147–154 | Cite as

Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes

  • Frank GrünhageEmail author
  • Matthias Jungck
  • Christoph Lamberti
  • Christine Berg
  • Ursula Becker
  • Hildegard Schulte-Witte
  • Dominik Plassmann
  • Nils Rahner
  • Stefan Aretz
  • Nicolaus Friedrichs
  • Reinhard Buettner
  • Tilman Sauerbruch
  • Frank Lammert
Original Article



About 20% of colorectal cancer (CRC) patients show some kind of familiarity, which might be caused by yet unknown combinations of low penetrance susceptibility genes. We aimed to identify genetic factors for familial CRC (fCRC) in a unique study design that includes phenotypic extremes as represented by fCRC cases and ‘hyper-normal’ controls without CRC history and no adenomatous polyps on colonoscopy.

Materials and methods

Candidate gene variants were determined by allele-specific amplification (SLC10A2 c.169C>T and c.171G>T) and restriction fragment length polymorphism assays (CCND1 c.870A>G; CDH1 –160C>A; TP53 R72P; VDR T2M). In total, 98 patients with fCRC, 96 patients with sporadic CRC, and 220 hyper-normal controls were included.


The minor allele of the CDH1 –160C>A polymorphism occurred significantly more often in controls compared to fCRC cases (OR = 0.664; p = 0.042). Homozygosity of the minor allele was significantly associated with affiliation to the control group (OR = 0.577; p = 0.029), indicating that both heterozygous and homozygous carriers of the common allele are at-risk for CRC. With respect to the CCND1 c.870A>G mutation, comparison of fCRC and sporadic CRC cases showed that A/A homozygosity was more common than G/G homozygosity among fCRC patients compared to controls (OR = 2.119; p = 0.045). However, no differences in allele or genotype frequencies were detected between sporadic CRC cases and controls, and no associations were observed for SLC10A2, TP53, and VDR polymorphisms.


We report a potential association of variants in the CCND1 and CDH1 genes with fCRC using a unique study design with phenotypic extremes.


Colorectal cancer Heritability Susceptibility 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Frank Grünhage
    • 1
    Email author
  • Matthias Jungck
    • 1
  • Christoph Lamberti
    • 1
  • Christine Berg
    • 1
  • Ursula Becker
    • 1
  • Hildegard Schulte-Witte
    • 2
  • Dominik Plassmann
    • 2
  • Nils Rahner
    • 3
  • Stefan Aretz
    • 3
  • Nicolaus Friedrichs
    • 4
  • Reinhard Buettner
    • 4
  • Tilman Sauerbruch
    • 1
  • Frank Lammert
    • 1
  1. 1.Department of Internal Medicine IUniversity Hospital Bonn, University of BonnBonnGermany
  2. 2.Outpatient Clinics for Gastroenterology and HepatologyBonnGermany
  3. 3.Institute of Human GeneticsUniversity Hospital Bonn, University of BonnBonnGermany
  4. 4.Institute for PathologyUniversity Hospital Bonn, University of BonnBonnGermany

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