Familial Cancer

, Volume 10, Issue 3, pp 605–616

Familial colorectal cancer: eleven years of data from a registry program in Switzerland


  • Michal Kovac
    • Research Group Human Genetics, Department of BiomedicineUniversity of Basel
  • Endre Laczko
    • Functional Genomics CenterUniversity of Zurich
  • Ritva Haider
    • Institute of Molecular Cancer ResearchUniversity of Zurich
  • Josef Jiricny
    • Institute of Molecular Cancer ResearchUniversity of Zurich
  • Hansjakob Mueller
    • Research Group Human Genetics, Department of BiomedicineUniversity of Basel
    • Research Group Human Genetics, Department of BiomedicineUniversity of Basel
    • Institute of Molecular Cancer ResearchUniversity of Zurich

DOI: 10.1007/s10689-011-9458-6

Cite this article as:
Kovac, M., Laczko, E., Haider, R. et al. Familial Cancer (2011) 10: 605. doi:10.1007/s10689-011-9458-6


Deleterious germ-line variants involving the DNA mismatch repair (MMR) genes have been identified as the cause of the hereditary nonpolyposis colorectal cancer syndrome known as the Lynch syndrome, but in numerous familial clusters of colon cancer, the cause remains obscure. We analyzed data for 235 German-speaking Swiss families with nonpolyposis forms of colorectal cancer (one of the largest and most ethnically homogeneous cohorts of its kind) to identify the phenotypic features of forms that cannot be explained by MMR deficiency. Based on the results of microsatellite instability analysis and immunostaining of proband tumor samples, the kindreds were classified as MMR-proficient (n = 134, 57%) or MMR-deficient (n = 101, 43%). In 81 of the latter kindreds, deleterious germ-line MMR-gene variants have already been found (62 different variants, including 13 that have not been previously reported), confirming the diagnosis of Lynch syndrome. Compared with MMR-deficient kindreds, the 134 who were MMR proficient were less likely to meet the Amsterdam Criteria II regarding autosomal dominant transmission. They also had primary cancers with later onset and colon-segment distribution patterns resembling those of sporadic colorectal cancers, and they had lower frequencies of metachronous colorectal cancers and extracolonic cancers in general. Although the predisposition to colorectal cancer in these kindreds is probably etiologically heterogeneous, we were unable to identify distinct phenotypic subgroups solely on the basis of the clinical data collected in this study. Further insight, however, is expected to emerge from the molecular characterization of their tumors.


ColorectumFamilial cancerLynch syndromeMismatch repairSwitzerland



Microsatellite instability




Amsterdam criteria II


Revised Bethesda guidelines


Mismatch repair


Multiplex-ligation dependent-probe amplification


Familial colorectal cancer type-X


Hereditary nonpolyposis colon cancer


Familial adenomatous polyposis

MMR-deficient or-proficient FCC

Mismatch repair deficient or proficient, familial colorectal cancer

Supplementary material

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Supplementary material 1 (XLS 49 kb)
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Supplementary material 2 (XLS 54 kb)
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Supplementary material 3 (XLS 54 kb)
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Supplementary figure 1 (JPG 881 kb)

Copyright information

© Springer Science+Business Media B.V. 2011