TY - JOUR
T1 - The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype
AU - Meijers-Heijboer, Hanne
AU - Wijnen, Juul
AU - Vasen, Hans
AU - Wasielewski, Marijke
AU - Wagner, Anja
AU - Hollestelle, Antoinette
AU - Elstrodt, Fons
AU - Van Den Bos, Renate
AU - De Snoo, Anja
AU - Fat, Grace Tjon A.
AU - Brekelmans, Cecile
AU - Jagmohan, Shantie
AU - Franken, Patrick
AU - Verkuijlen, Paul
AU - Van Den Ouweland, Ans
AU - Chapman, Pamela
AU - Tops, Carli
AU - Möslein, Gabriela
AU - Burn, John
AU - Lynch, Henry
AU - Klijn, Jan
AU - Fodde, Riccardo
AU - Schutte, Mieke
N1 - Funding Information:
We are indebted to the members of the families with colorectal cancer and families with breast cancer for their participation in this research. The families with colorectal cancer were recruited by CAPP (chaired by J. Burn), also involving A. Alonso, M. Barker, A. Barrows, M. Bisgaard, T. Bishop, D. Eccles, P. Morrison, V. Murday, J. Sampson, and S. Werner, and by STOET (chaired by H. Vasen), also involving J. Kleibeuker, F. Menko, F. Nagengast, and M. Velthuizen. The families with breast cancer were ascertained through the Rotterdam family cancer clinic, also involving C. Bartels, A. van Geel, D. Halley, C. van der Meer, M. Menke-Pluymers, R. Oldenburg, C. Seyneave, M. Tilanus-Linthorst, M. van Veghel-Plandsoen, and M. van Vliet. We thank Sheila Seal and Rita Barfoot for their support with the BRCA1 and BRCA2 mutational screens. This work was supported by the Erasmus MC Revolving Fund, Dutch Cancer Society, EU Biomed 1/2 Programs, Bayer Corporation, National Starch Corporation, UK Medical Research Council, and UK Cancer Research.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038406108&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038406108&partnerID=8YFLogxK
U2 - 10.1086/375121
DO - 10.1086/375121
M3 - Article
C2 - 12690581
AN - SCOPUS:0038406108
VL - 72
SP - 1308
EP - 1314
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -