Wagner, K: Search for Breast Cancer Susceptibility Genes

Breast Cancer is the most common cancer in Western women and represents 28% of female cancer deaths. During the last decades, research has revealed cancer as a complex heterogeneous disease triggered by dynamic changes in the genome. The work in this dissertation summarizes the investigation of polymorphisms in the GH1/IGF-1 axis in relation to breast cancer risk by means of the planning and conducting of case-control studies. Many findings were novel and they reflected the complexity of the gene regulation along the GH1/IGF-1 pathway. In summary, the studied polymorphisms were mainly associated with a decreased breast cancer risk. This lead to the suggestion that genetic variants in the GH1/ IGF-1 axis do not increase the mitogenic and antiproliferative features of the pathway, but rather protect the cells from proliferation. The study contributes to the world-wide effort of identification of low-penetrance genetic variants, which may be useful tools for prevention, prognosis and planning of individual therapy.

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