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.

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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
J.G.M. Klijn (Jan)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Wasielewski, M. (2009, April 29). CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer. Retrieved from