Genetic determinants of breast cancer susceptibility in the Byelorussian population Von der Naturwissenschaftlichen Fakultät der Gottfried Wilhelm Leibniz Universität Hannover zur Erlangung des Grades Doktor der Naturwissenschaften Dr. rer. nat. genehmigte Dissertation von Natalia Valerjevna Bogdanova geboren am 22. Oktober 1978 in Minsk (Weissrussland) 2008 Referent: Professor Dr. Jürgen Alves Korreferent: Professor Dr. Ekkehard Dikomey Tag der Promotion: 21. August 2008 I dedicate my work to the memory of excellent researcher, outstanding person, my teacher and friend Dr. Sergej Pavlovich Festchenko. Abstract I Abstract Breast cancer is the most common lethal malignancy of women all over the world. Mutations in known breast cancer susceptibility genes including BRCA1 and BRCA2 mutations can confer a high life-time risk for breast cancer up to 85%, whereas CHEK2, ATM and NBN mutations are proposed to be associated with a lower penetrance. The products of these genes are involved in DNA double-strand break signaling and repair, and considerable efforts have been made during the past years to identify the mutational spectra of these genes in familial and sporadic breast cancer.