One-Carbon Glutathione Metabolism | © dkfz.de

The Division of Preventive Oncology has one major research area in the Molecular Epidemiology of Cancer, with emphasis on colorectal cancer. Molecular epidemiology utilizes state-of-the-art techniques to measure biomarkers and genetic factors, and health behaviors and investigate their joint effects on disease risk. The Division is largely focusing on research in diet and cancer, as well as inflammation/DNA damage and cancer, but studies also other biologic pathways and mechanisms.

For example, high intakes of vegetables are protective against colorectal cancer and one key component of plants is the B-vitamin folate. Inherited genetic variability is common, and all humans show small differences in their enzymes and other proteins (genetic polymorphisms). For example, genetic polymorphisms in the folate biochemical pathway can affect how people process folate and that in turn will influence their disease risk (gene-diet interaction). Further, folate is critical for providing methyl groups, which are in turn needed for epigenetic regulation of gene expression and gene silencing. Thus, epigenetic biomarkers are part of the Division’s research. With respect to folate intake, we have also created a mathematical simulation model of folate-mediated one-carbon metabolism (In Silico Metabolism, ISM, which is freely available). This simulation model incorporates information from biochemistry and regulatory mechanisms to make predictions on metabolic endpoints. More information and software requests can be made here.

Inflammation is another key pathway relevant to carcinogenesis. Aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal carcinogenesis and thus aid in cancer prevention. However, genetic factors that alter the uptake or excretion of NSAIDs or the functioning of prostaglandin synthesis (the pathway targeted by NSAIDs) may alter the responsiveness to these drugs (gene-drug interaction). Thus only a subset of individuals may benefit, while others might be at increased risk of adverse side effects. The Division studies how inherited genetic variation in inflammation affects disease risk and alters the responsiveness to NSAIDs. Researchers of the Division also study other pathways of specific relevance to carcinogenesis.

In addition to these hypothesis-driven approaches, that involve the study of a specific candidate pathway, the Division is also actively participating in screening the entire genome for genetic variation and studying the relevance to disease risk and cancer survival. These genome-wide association studies (GWAS) are collaborations with researchers in Heidelberg and the Fred Hutchinson Cancer Research Center.