A new program at UCLA's Jonsson Cancer Center and the School of Public Health will seek to discover subtle variations in the human genetic blueprint that predispose some individuals to develop cancer after contact with environmental pollutants.

The program will explore, for example, why some individuals exposed to second-hand cigarette smoke develop lung cancer, while others do not. Bringing together the best environmental researchers and molecular biologists at UCLA, the program seeks to shed new light on how pollutants interact with genetics to cause a variety of cancers.

The program will be headed by Dr. Robert H. Schiestl, UCLA professor of pathology, environmental health and radiation oncology.

"We'll investigate the molecular mechanism by which environmental agents such as air pollution, pesticides and radiation cause cancer and why a certain sub-population of people are more sensitive to these environmental exposures than the general population," Schiestl said.

"With knowledge about the mechanism of this interaction between environmental exposure and genetic predisposition, it's our goal to develop improved biomarkers of exposure, to identify people at increased risk and to design nutritional and chemical interventions to counteract the development of cancer, especially in those with increased sensitivity."

The environmental genomics program will focus on six research projects that seek to:

• Characterize genetically the effects of air pollution particles on the makeup of human cells.
• Understand the relationship of environmental exposures and a nonsmoker's susceptibility to lung cancer.
• Identify the specific protein that prevents a cancer-causing enzyme from activating potent carcinogens found in smog, cooked foods and cigarette smoke.
• Investigate the molecular mechanism responsible for higher incidence of prostate cancer for men exposed to pesticides in California.
• Characterize genetically the molecular basis of hypersensitivity to radiation treatment in certain cancer patients.
• Characterize the mechanism that makes boron a dietary element that appears to prevent or reduce the risk of prostate cancer.

"This program promises to be a unique effort that we hope will unravel many of the mysteries surrounding the interaction of genes and environment in the development of cancer," said Judith C. Gasson, a scientist and director of UCLA's Jonsson Cancer Center.

Cancer occurs when changes in our genetic blueprint, or DNA, cause certain genes to become altered in cells, which then grow out of control. In some people, exposure to environmental pollutants may trigger these changes or genetic mutations.

"Before we had the new tools of the genome revolution, disease was considered to be either environmentally or genetically caused," said Linda Rosenstock, dean of the School of Public Health, who will oversee the new program. "But now we know that most diseases are the result of an interaction between genetics and the environment. At UCLA, we are fortunate to have the top scientific minds in both environmental research and molecular biology, which uniquely positions us to tackle these emerging issues."

Understanding the processes and genetic alterations involved in the development of various cancers has already resulted in targeted therapies that attack what is broken in cancer cells, leaving healthy tissues alone and resulting in less toxic treatments for patients. The same promise holds true for the environmental genomics program, Rosenstock said.

"Perhaps by understanding the genetic risks posed by environmental pollutants, we can tailor drugs to help prevent cancer," she said. "Or, more likely, we can try to control the environmental factors for those people at risk for cancer."

About 95 percent of the nearly 2.5 million Americans who will be diagnosed with cancer this year have no known genetic predisposition to the disease. Researchers believe these people develop malignancies due to complex interactions between their genes and their environment. If scientists can uncover the chemical and biological cascade that results in cancer, they can potentially stop the disease before it occurs. The goal is to discover what specific combination of an individual's genetics and factors such as diet, air pollution, exposure to tobacco or sensitivity to sunlight result in disease.

"The key to the future is to understand why certain people develop certain cancers," Rosenstock said. "Through this kind of research, merging environmental factors and molecular genetics, we may be able to find the answers." SOURCE:
University of California, Los Angeles (http://www.mednet.ucla.edu)