Researchers at Emory’s Winship Cancer Institute have earned a five-year, $7.4 million grant from the National Institute of Environmental Health Sciences (NIEHS), supporting their work examining the links between oxidative stress and colorectal cancer, the second deadliest cause of cancer in the United States. The NIEHS is part of the National Institutes of Health.
Diet, environmental pollutants, radiation and drugs can all influence the body’s oxidative stress level, says Paul Doetsch, PhD, professor of biochemistry, radiation oncology, and hematology and oncology at Emory University School of Medicine and the grant’s principal investigator.
Oxidative stress comes from an imbalance between reactive oxygen species and the body’s ability to detoxify them. Reactive oxygen species can drive cancer formation by damaging cells’ DNA, leading to mutations and genetic instability that unleash out-of-control growth.
"Understanding the links between oxidative stress and colon cancer could help doctors predict colon cancer risk and design prevention regimes," says Doetsch, who is also deputy director for basic research at Winship Cancer Institute.
At the same time, major sources for reactive oxygen species exist within the body, he says. Internal sources of reactive oxygen species include mitochondria, the body’s mini-power plants, and NADPH oxidase, a chemical weapon the immune system uses to deploy reactive oxygen species against bacterial and fungal invaders.
The NIEHS grant will fund several projects studying the contribution of mitochondria and NADPH oxidase to oxidative stress and cancer, and the ability of DNA damage caused by oxidative stress to influence colon cancer formation.
As an example, professor of pathology and laboratory medicine David Lambeth, MD, PhD, and colleagues recently showed that NADPH oxidase is turned on abnormally in colon cancer cells. Their work was published in the International Journal of Cancer in July.
Noting that the new grant renews and builds upon previous support from the NIEHS, Doetsch says: "We’ve been able to advance our work from the simpler models we started with to the more complex mammalian systems. This is the anchor for Winship's Cancer Genetics and Epigenetics scientific program." http://www.cancer.emory.edu/index.cfm?pageid=36
Participating Emory faculty include Doetsch, Lambeth, Gray Crouse, PhD, professor of biology and Yoke Wah Kow, PhD, professor of radiation oncology. Also participating is Gerald Shadel, PhD, a former Emory faculty member who is now a professor of pathology and genetics at Yale University School of Medicine.
Reference: Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras. E. Laurent et al, Int J Cancer 123: 100-107.