WSU scientist wins federal grant to explore metabolism pathways, tobacco carcinogens

A Washington State University researcher has received a $2.6 million federal grant to study the body's ability to keep tobacco smoke components from causing cancer.

Philip Lazarus, a distinguished professor and chair of pharmaceutical sciences, will use the National Institute of Health grant to look for genetic markers in enzymes that indicate an increased risk of developing lung, head and neck cancers from exposure to the carcinogens commonly found in tobacco smoke.

UGT proteins are a major family of enzymes in the body that detoxify and eliminate carcinogens. They bind sugar molecules to carcinogenic targets, like polycyclic aromatic hydrocarbons from tobacco smoke, to make them more water soluble and easier for the body to excrete.

"The liver is the main filter of the body, but localized metabolic detoxification and elimination also occurs in tissues outside the liver," said Lazarus. "For lung and head and neck tissue, this may be an important mechanism for reducing internal carcinogen exposure."

In earlier work, Lazarus found genetic variants of certain UGT enzymes that reduced the body's ability to detoxify carcinogens, increasing the risk of cancer. The new study will focus on similar UGT enzymes recently identified as important in carcinogen detoxification.

The research team will also look at different forms of UGT proteins expressed by the UGT gene produced by a process called "alternative splicing." These UGT forms may not work as enzymes and even appear to knock out the detoxifying activity of normal UGT proteins.

The UGT enzymes play a major role in drug response and metabolism, so a better understanding of the detoxification pathway will help researchers develop personalized approaches to medicine and the treatment of disease.

"This could be important in how genes are regulated, which means it could be a 'new horizon' for science as it relates to how we understand susceptibility to cancer," said Lazarus. "My research examines why some people get cancer and some don't, and how we can use differences in individual susceptibility to develop personalized treatments."

Source: Washington State University