Cancer Prevention and Intervention

cancer chemoprotection program

The Cancer Prevention and Intervention program identifies previously unstudied phytochemicals (chemicals from plants that may affect health) and develops existing phytochemicals as supplements that can protect against different types of cancer, including colorectal, breast, prostate, and liver cancer. We are interested in understanding the molecular mechanisms responsible for the anticancer effect of certain dietary compounds, such as tea catechins, sulforaphane, indole-3-carbinol, allyl sulfides, chlorophyll, and zinc. We are also interested in epigenetic effects that modulate cancer risk across the lifespan, from the fetus to adulthood.

Faculty involved: Emily Ho, Ph.D., Gerd Bobe, Ph.D., M.P.H., and David E. Williams, Ph.D.

Cancer Chemoprotection for the Fetus and Infant

Principal Investigator: David E. Williams, Ph.D.

Cancer chemoprotection by dietary micronutrients, including vitamins and phytochemicals, is a very important component of our “war on cancer.” Thirty to forty percent of cancers worldwide are preventable by optimizing diet, physical activity, and maintenance of appropriate body weight. Estimates are that cancer rates can be significantly reduced in lung (20-33%), stomach (66-75%), breast (33-50%), colon/rectum (66-75%), mouth/pharynx (33-50%), and liver (33-66%) by simple lifestyle choices, mostly related to diet, including adoption of a diet rich (400-800 g daily) in a variety of fruit and vegetables.

Few cancer prevention studies targeting the fetus or infant have been conducted, even though this early developmental stage is highly sensitive to cancer from chemicals crossing the placenta or transferred via mother’s milk. Our laboratory focuses on the phytochemicals indole-3-carbinol (I3C) and sulforaphane, found in cruciferous vegetables (e.g., broccoli, cauliflower, and Brussels sprouts). Initial studies utilized pregnant rodent models to ascertain potency, efficacy, and mechanisms of action of these phytochemicals, when added to the diet of the pregnant or lactating animal, in protecting the offspring from developing cancer later in life (even if they don’t eat their vegetables). We have repeatedly demonstrated that I3C in the maternal diet markedly protects the offspring from cancer from exposure in utero to environmental carcinogens. Ongoing studies will provide new insights into underlying mechanisms by which maternal fruit and vegetable intake protects against cancer in offspring. We plan to move into translational studies with humans, correlating maternal diet, carcinogen exposure, and risk to the fetus or infant.

Dietary Interventions for Cancer Prevention

Principal Investigator: Gerd Bobe, Ph.D., M.P.H.

My laboratory focuses on identifying biomarkers in humans and parallel animal models that are associated with colorectal and pancreatic cancer and can be modified by diet and dietary supplements, including micronutrients and polyphenols. Colorectal cancer is an important public health problem, annually leading worldwide to over 500,000 deaths and in the US nearly 150,000 new cases and 50,000 deaths. Dietary change, both feasible and safe, represents a viable strategy for preventing colorectal cancer; however, dietary intervention trials often showed no protection. There is a need for biomarkers of exposure, risk, and response to dietary interventions. Such biomarkers will provide crucial data to 1) identify individuals at increased risk or early stages of colorectal carcinogenesis, 2) measure compliance with dietary interventions, and 3) predict individuals most likely to benefit from a long-term dietary intervention (i.e., personalized cancer prevention).

In a collaborative project, we have been linking prospective human cohort and nutrition studies at the National Cancer Institute with food databases to identify diets and dietary components, most notably flavonols, with promise of efficacious cancer prevention. For dietary components showing efficacy, we have been identifying biomarkers of exposure, risk, and early dietary response, especially interleukin 6, through parallel human intervention and animal model studies in serum, feces, and tissue. The functional significance of the identified molecular targets in carcinogenesis will be tested using cell culture and transgenic mouse studies. The goal is to use the identified molecular targets and biomarkers in clinical trials to test the efficacy of diets and dietary supplements for cancer prevention.

Zinc and Antioxidants in Cancer Chemoprevention

Principal Investigator: Emily Ho, Ph.D.

My research focuses on understanding the molecular mechanisms by which nutrient status affects the initiation and/or progression of chronic disease states like cancer. Low intake of several nutrients, such as zinc, could be a major risk factor for several types of cancer, as suggested by both epidemiological and laboratory studies. The main areas of interest in my laboratory are the function of zinc across the lifespan and dietary influences on prostate cancer development. Zinc is a component of over 300 proteins, including DNA-binding proteins with zinc fingers, Cu/Zn superoxide dismutase, and several proteins involved in DNA repair, such as p53, which is mutated in half of human tumors. We have found that deficits in zinc intake could also have a major impact on an individual’s susceptibility to DNA damage and risk for developing cancer due to zinc’s function as an antioxidant and its role in DNA damage response. We are also interested in the effects of zinc during development and in the aging immune system. Prostate cancer is one of the leading causes of cancer-related deaths in men. The prostate contains the highest concentration of zinc in the body, and low zinc intake may increase the risk for prostate cancer. We have found that other dietary compounds, especially those found in traditional Asian diets, such as soy, teas, and cruciferous vegetables like broccoli, can limit prostate cancer development. A new, exciting interest in the laboratory is to understand the interaction between diet and epigenetic alterations in histone structure and prostate cancer risk.