CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer
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.
|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|
Wasielewski, M.. (2009, April 29). CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/15676