TUESDAY, March 30, 2004 (HealthDayNews) -- Some studies have suggested that women who smoke are more susceptible to lung cancer than their male counterparts, and now new mouse research may help explain why.

A Fox Chase Cancer Center researcher and her colleagues have identified a genetic alteration that occurred up to 13 times more frequently in the lung tissue of mice exposed to tobacco smoke than those in a control group. Even after just three weeks, the mice who breathed tobacco smoke had elevated levels of the enzyme CYP1B1, which activates estradiol, one of the body's natural estrogen hormones.

The discovery points to a possible link between changes in that hormone and lung cancer.

"It can help us understand one of the factors that can be involved in the susceptibility of women who smoke and develop more cancer," says study author Sibele I. Meireles. Since this alteration is present in human lung tumors, it could also be a target for new treatments to prevent lung cancer in smokers, she adds.

"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," Meireles says in a statement.

Her finding was presented March 29 at the American Association of Cancer Research annual meeting in Orlando, Fla.

Lung cancer is the leading cause of cancer death among women in the United States, according to the American Cancer Society. National statistics show the incidence of lung cancer is still increasing among women, although the rate of increase has slowed.

This study suggests there may be a gender difference in the development of lung cancer.

To test the effects of cigarette smoke on gene expression, Meireles and her colleagues exposed female mice to smoke six hours a day, five days a week, for a total of eight weeks. The experiment involved a total of 30 mice, including 12 animals in the control group.

The team analyzed ribonucleic acid (RNA) from the lungs of the mice to determine which genes were being expressed. RNA is involved in carrying genetic information from the DNA and translating it into proteins.

The authors identified a total of 53 smoking-induced genetic alterations but honed in on the 13-fold overexpression of CYP1B1.

"This specific one caught our attention because of the high levels of changes," Meireles says.

George Leikauf, a professor of environmental health and director of toxicology at the University of Cincinnati, says the study is limited by its small sample size and its exclusion of male mice. More data would be needed to prove a connection between the enzyme CYP1B1 and lung cancer.

"If it's different between male and female mice, that would be very interesting data," he adds.

Margie L. Clapper, director of chemoprevention research at Fox Chase, says the experiment was rather labor-intensive, but agrees further studies will be needed to validate the results. In fact, the next step is compare male and female mice.

More information

The American Lung Association and the American Cancer Society can tell you more about lung cancer.

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