The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype

Hanne Meijers-Heijboer, Juul Wijnen, Hans Vasen, Marijke Wasielewski, Anja Wagner, Antoinette Hollestelle, Fons Elstrodt, Renate Van Den Bos, Anja De Snoo, Grace Tjon A Fat, Cecile Brekelmans, Shantie Jagmohan, Patrick Franken, Paul Verkuijlen, Ans Van Den Ouweland, Pamela Chapman, Carli Tops, Gabriela Möslein, John Burn, Henry T. LynchJan Klijn, Riccardo Fodde, Mieke Schutte

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160 Scopus citations


Because of genetic heterogeneity, the identification of breast cancer-susceptibility genes has proven to be exceedingly difficult. Here, we define a new subset of families with breast cancer characterized by the presence of colorectal cancer cases. The 1100delC variant of the cell cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380 families with non-HBCC (P <.001), thus providing genetic evidence for the HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s). The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene.

Original languageEnglish
Pages (from-to)1308-1314
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - May 1 2003


All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Meijers-Heijboer, H., Wijnen, J., Vasen, H., Wasielewski, M., Wagner, A., Hollestelle, A., Elstrodt, F., Van Den Bos, R., De Snoo, A., Fat, G. T. A., Brekelmans, C., Jagmohan, S., Franken, P., Verkuijlen, P., Van Den Ouweland, A., Chapman, P., Tops, C., Möslein, G., Burn, J., ... Schutte, M. (2003). The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. American Journal of Human Genetics, 72(5), 1308-1314.