Approximately 15-25% of breast cancers are identified in women with a family history of breast cancer. Yet, germline mutations in the currently known breast cancer susceptibility genes account for only one-third of familial breast cancer cases. In 2002, our research group had identified the CHEK2 1100delC mutation as a breast cancer susceptibility allele. It was estimated that this mutation confers an approximately 2-fold increased breast cancer risk for female CHEK2 1100delC carriers. Although this 2-fold increased breast cancer risk had classified the CHEK2 1100delC mutation as a moderate-risk breast cancer susceptibility allele, the mutation typically was more prevalent among breast cancer families with a high-risk breast cancer inheritance pattern. Also, the CHEK2 1100delC mutation did not completely segregate with the breast cancer phenotype in the high-risk breast cancer families. Together, these observations suggested the presence of additional cance! r susceptibility alleles in CHEK2 1100delC families. This thesis has focused on three topics related to the CHEK2 gene and in particular the CHEK2 1100delC mutation: analysis of the CHEK2-p53 tumor suppressor pathway by mutation analysis of both genes in human breast cancer cell lines; evaluation of the association of CHEK2 1100delC with male breast cancer and colorectal cancer; and identification of genes involved in the polygenic CHEK2 cancer model by using a candidate gene approach.

Additional Metadata
Keywords CHEK2, breast cancer, colorectal cancer
Promotor J.G.M. Klijn (Jan)
Publisher Erasmus University Rotterdam
Sponsor EMC, Dutch Cancer Society, J.E. Jurriaanse Stichting, Amgen BV, AstraZeneca BV, Bristol-Meyers Squibb BV, Merck Serono BV, MRC-Holland BV, Wyeth Pharmaceuticals BV, GlaxoSmithKline BV
ISBN 978-908559-505-2
Persistent URL
Wasielewski, M. (2009, April 29). CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer. Erasmus University Rotterdam. Retrieved from