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.

Additional Metadata
Keywords *Mutation, *Phenotype, *Protein-Serine-Threonine Kinases, Adult, Breast Neoplasms/*genetics, Colorectal Neoplasms/*genetics, DNA Mutational Analysis, Family, Female, Gene Frequency, Genes, cdc, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Pedigree, Protein Kinases/*genetics, Research Support, Non-U.S. Gov't
Persistent URL hdl.handle.net/1765/8489
Journal American Journal of Human Genetics
Citation
Meijers-Heijboer, E.J, Moslein, G, Lynch, H, Wasielewski, M, Fodde, R, Wagner, A, … Hollestelle, A. (2003). The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. American Journal of Human Genetics. Retrieved from http://hdl.handle.net/1765/8489