Tuesday, March 31, 2009

Why Cancer Strikes Some

It's a conundrum that puzzles doctors and patients alike: one person smokes a few cigarettes per week in college and contracts lung cancer in middle age, while another person smokes a pack a day his whole life -- and lives to age 90.

A new program announced last week by the National Institutes of Health aims to unravel such mysteries by precisely measuring the role that environmental agents, such as pesticides and solvents, play in common diseases, including cancer, asthma, and autism.

A major part of the program will fund the development of technologies to monitor personal environmental exposures and to determine how those exposures interact with an individual's genetic makeup to increase the risk for disease. Scientists hope these technologies will allow doctors to determine who is at risk early on, and thus be able to intervene soon enough to prevent serious damage.

The NIH has designated $88 million for the period 2007-10 to fund research both inside and outside the institute. The money will go toward development of wearable sensors that measure exposure to environmental toxins, such as solvents, pesticides, and heavy metals.

The funds will also support the development of sensors to determine if exposure to toxins triggers biochemical pathways linked to disease, such as inflammation or cell death, in some individuals. Ultimately, these technologies will be incorporated into genetic studies to understand the link between genes, the environment, and disease.

Initially, the sensors would be used in population studies of disease. But David Schwartz, director of the National Institute of Environmental Health Sciences (part of the NIH), envisions a day when everyone would wear a sensor that measured levels of key chemicals. An individual's doctor could then read the information and determine if the patient had been exposed to chemicals and therefore was at risk of developing a disease.

The role of environmental toxins in human disease and death has been a major issue in both the public health and legal arenas. Scientists often have difficulty determining if a reported increase in disease, such as a cancer cluster, is linked to a specific factor in the environment. Emerging technologies that could accurately measure exposure and individual response to different chemicals could clarify these often contentious cases.

New technologies could also help scientists understand some medical mysteries of our time -- such as rising asthma rates, which have doubled in the last two decades. Since the publication of the human genome sequence in 2003, scientists have focused enormous amounts of energy on the genetic basis of disease. "But genes don't tell the whole story," says Schwartz. "The recent increases in asthma, diabetes, and autism are not due to changes in our genome over last couple of decades. These major shifts point to the role our diet, activity levels, and environment play in disease."

"Scientists can now precisely measure genetic variation between individuals, but we can't accurately measure the individual variation in exposure or response to exposure...when faced with environmental challenges," Schwartz says. The new program hopes to fill that gap.

This timely program will take advantage of the explosion of information about the genome sequence, says Gerald N. Wogan, professor of chemistry and biological engineering at MIT. For example, scientists already know that people carry different forms of enzymes that detoxify chemicals, and that specific variants increase the risk of bladder cancer. But these new tools would allow scientists to do this kind of research on a much broader scale, he says.

Esteban González Burchard, a scientist at the University of California, San Francisco, believes that these kinds of tools will also help researchers understand complex diseases, such as asthma. His team, for instance, has shown that people with a particular genetic background are more likely to develop asthma when exposed to secondhand smoke. But the environmental contribution to asthma is probably even more complex, he says, with factors such as socioeconomic status also playing a role. And new technologies could help scientists sort out these complex factors.


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