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Molecular Epidemiology of Cancer Development and Cancer Prognosis

One of the Ulrich group’s research areas is 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 Ulrich group employs a variety of laboratory techniques including multiple –omic strategies (metabolomic, genomic, proteomic, epigenomic and studies of the gut microbiome). The group focuses on research in diet, energy balance, inflammation, DNA damage and cancer, but studies also other biologic pathways and mechanisms.

A major research area focuses on the nutrient folate and its role in one-carbon metabolism. 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. Folate is also critical to DNA synthesis and is a major target of chemotherapeutic agents. One of the recently funded studies of Dr. Ulrich focusing on folate and related pathways is the FOCUS consortium.

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 Ulrich group studies how inherited genetic variation in inflammation affects disease risk and alters the responsiveness to NSAIDs and has published extensively in this area. Most recently, we showed using a metabolomics approach that aspirin reduces 2-hydroxyglutarate, a metabolite that causes cancer.

Obesity can also be a major driver of carcinogenesis (in particular for colorectal, esophageal, liver and breast cancer after menopause), while physical activity is preventive for colorectal and postmenopausal breast cancer. We are investigating multiple components of adiposity, physical activity and "energy balance“ and their relation to cancer development and progression. For example, we have used metabolomics to discern differences in adipose tissue from inside the body (visceral adipose tissue) to that below the skin (subcutaneous adipose tissue) and shown that there are major differences in inflammatory and other characteristics. Weight loss through exercise and diet can directly impact the adipose tissue. We also use accelerometry and other state-of-the art tools to measure physical activity and test associations with other factors, including vitamin D levels.

The Ulrich group also uses the methodology of molecular epidemiology in research on Cancer Prognosis, Survivorship and Pharmacogenetics.