Hormonal factors and genetic modification of colorectal cancer risk

Women are less likely to develop colorectal cancer than men, which may in part be due to hormonal differences. The DACHS study and other studies have shown that use of menopausal hormone therapy is associated with a reduced colorectal cancer risk. It is possible that the development of colorectal cancer is influenced by endogenous hormones as well as exogenous hormones.

To explore this relationship we investigate variants in candidate hormone related genes, which may modify the association of menopausal hormone therapy with colorectal cancer. The effect of genetic variants on colorectal cancer risk is initially assessed and then the effect of menopausal hormone use on colorectal cancer risk in genetically defined subgroups. Promising findings will be evaluated in independent study populations.

Additionally, a genome-wide analysis of gene-environment interaction with menopausal hormone therapy will be carried out as well as a pathway analysis including among others hormone-metabolism pathways. Both analyses will be conducted in collaboration with the "Genetics and Epidemiology of Colorectal Cancer Consortium" GECCO.

Cooperation: Division of Clinical Epidemiology and Aging Research (DKFZ), Division of Molecular Genetic Epidemiology (DKFZ), Institute of Pathology Heidelberg, Institute of Clinical Molecular Biology (Schleswig-Holstein University Hospital), Colon Cancer Genetics Group (MRC Human Genetics Unit, Western General Hospital, Edinburgh), GECCO (Fred Hutchinson Cancer Research Center Seattle, Washington, USA)

Funding: German Federal Ministry of Education and Research (BMBF, grant number 01GS08181) to the Colorectal Cancer Network (CNN), in the National Genome Research Network (NGFN+); NIH (USA) grant to GECCO 

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