December 20, 2011
The Foundation is proud to highlight the breast cancer research of Lauren Trepanier, DVM, PhD, a professor at the University of Wisconsin-Madison’s School of Veterinary Medicine. Dr. Trepanier received a two-year grant from the Foundation in spring 2008 to examine whether specific enzymes present in the human breast are associated with breast cancer risk.
What led you to the field of breast cancer research?
I began my career by studying adverse drug reactions, in particular sulfonamide hypersensitivity (sulfa drug allergy). We wanted to understand why these drug reactions occur in certain patients, so we were studying the pathways that the body uses to detoxify, or neutralize, these drugs. We found that humans use a key enzyme pathway (cytochrome b5 and its reductase) to detoxify sulfonamide drugs. We also found that we use this same pathway to neutralize certain environmental carcinogens that have been associated with breast and other cancers.
Tell us about your research examining the role of two enzymes, b5R and cyt b5, in eliminating cancer-causing metabolites in the breast and whether individual differences in these enzymes are associated with breast cancer risk.
The enzymes b5 (cytochrome b5) and b5R (cytochrome b5 reductase) neutralize cancer-causing (arylhydroxylamine) chemicals, which enter the body when we eat grilled meats or smoke cigarettes. These chemicals damage DNA and lead to altered cell growth and mammary cancer in animals. Diets high in grilled meats are risk factors for breast cancer in women, and while smoking has been associated with breast cancer risk in some studies, the link is more controversial. Human breast tissue and even breast milk contains DNA that has been damaged by these chemicals, but the amount of damage varies between women. So there are individual factors that modulate how two women may respond differently to the same chemical exposure.
We found that the b5/b5R detoxification pathway is present in human breast, with more than 70-fold differences in the ability to neutralize these arylhydroxylamine chemicals among individual women. We also found genetic defects in the b5/b5R detoxification pathway, which were significantly more common in African American women compared to Caucasians. We are now looking at the relationship between these genetic differences, smoking exposure and breast cancer, along with other genetic factors, in the Carolina Breast Cancer Study population, a large group of African American and Caucasian women that have been diagnosed with breast cancer. We hope to identify groups of women with high-risk genetic patterns that may have a higher likelihood of breast cancer in association with smoking.
How has receiving a Prevent Cancer Foundation grant impacted your research?
Funding from federal agencies is very difficult to obtain right now, with some government institutes funding less than 1 in 10 of grants that are submitted. So funding from private foundations is more important than ever for scientists to continue their work, and to train the next generation of scientists. The Prevent Cancer Foundation has been pivotal in our ability to apply the insights and research resources that we have acquired from studying the risk of adverse drug reactions, to the field of cancer risk.
Why is it important to fund research in the field of cancer prevention and early detection?
Cancer prevention is, of course, the ideal. Breast cancer rates are highest in industrialized countries, and families that move from low-risk to high-risk countries acquire a breast cancer risk of their new industrialized homes in as little as two generations. This points to an important role of environmental factors in the development of breast cancer. A better understanding of how environmental factors, such as diet and smoking, interact with in-borne genetic traits will improve the quality of individualized advice that can be provided to women about personal breast cancer risk prevention and monitoring.