Fox Chase Cancer Center researchers identify significant smoking-induced genetic alteration

03/19/04

Finding may help scientists understand why women smokers are more susceptibility to lung cancer

A Fox Chase Cancer Center researcher and her colleagues have identified a genetic alteration that occurs 13 times more frequently in lung tissue of mice exposed to tobacco smoke. The frequency of this genetic alteration and its role in estrogen metabolism could help researchers understand why women who smoke are more susceptible to lung cancer. These findings were presented today at the 95th Annual Meeting of the American Association for Cancer Research in Orlando, Fla.

The researchers found 53 smoking-induced genetic alterations in mice exposed to tobacco smoke compared to unexposed controls. The most notable finding was the 13-fold overexpression of the enzyme CYP1B1.

"Our research demonstrates that this alteration isn't present in the lung tissue prior to tobacco exposure," said Fox Chase researcher Sibele I. Meireles, Ph.D., lead author of the research. "Since we know this alteration is present in human lung tumors, it could be a target for chemopreventive intervention in people at high risk for lung cancer--in particular, active smokers."

Because CYP1B1 activates estradiol, one of the body's natural estrogen hormones, this finding could also help researchers understand more about why female smokers are more susceptible to lung cancer than male smokers.

"The overexpression of CYP1B1 poses an interesting question about gender differences in the development of lung cancer," said Meireles "We hadn't intended to look at gender differences in this study, but this finding about an enzyme so important to estrogen metabolism once again raises the issue of whether estrogen has a role in promoting lung cancer, as it does in breast and ovarian cancer."

The American Cancer Society estimates that 173,770 people will be diagnosed with lung cancer in 2004 and an estimated 160,440 people will die of the disease this year.

Meireles is a postdoctoral associate in the laboratory of cell biologist Margie L. Clapper, Ph.D., director of chemoprevention research at Fox Chase. In addition to Clapper, Meireles' co-authors include Fox Chase bioinformatician Radka Stoyanova, Ph.D., Bela Verma, M.S., a student at Robert Wood Johnson Medical School, and two investigators from the University of Kentucky, C. Gary Gairola, Ph.D., professor of tobacco and health research, and Ramesh C. Gupta, Ph.D., professor of toxicology and preventive health.

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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