Lung cancer gene has gender bias - Brief Article

Science News, Feb 5, 2000 by D.C.

Of all cancers, lung cancer causes the most deaths in the United States. Smoking leads to almost 90 percent of cases, but researchers have been unable to explain why among smokers, women seem to be 2 to 3 times as susceptible to the disease as men are.

A new study may help explain this gender bender. A gene for a protein that promotes lung cancer growth is more likely to be active in women than in men, says Sharon P. Shriver of Pennsylvania State University in State College.

Known as gastrin-releasing peptide receptor, or GRPR, the gene is not typically active in the lungs of nonsmokers, Shriver says. Tests of lung cancer cells, however, show that nicotine turns the gene on, she and her colleagues at the University of Pittsburgh report in the Jan. 5 JOURNAL OF THE NATIONAL CANCER INSTITUTE. The gene resides on the X chromosome. Therefore, women have twice as many copies of GRPR as men do and so are probably more susceptible to smoking's carcinogenic effects.

Shriver and her colleagues looked at normal lung tissue that had been removed from 38 women and 40 men during surgery related to lung cancer or another lung disease. Among the nonsmokers, 55 percent of the women and none of the men had active copies of the gene. Among people who had smoked less than the equivalent of a pack of cigarettes a day over 25 years, 75 percent of the women and 20 percent of the men had active GRPR copies, she says. In those who smoked more, about 70 percent of both men and women had an active GRPR in their lungs.

The incidence of lung cancer was 12 times higher for women with an active GRPR gene than for women with inactive genes. It was only 2.4 times higher for men with the active gene than for men without it, Shriver says. If further work bears out her findings, she says, GRPR activity might predict which people are most likely to develop cancer. "This kind of early marker for lung cancer is something we don't have right now," she says. Lung cancer is deadly because doctors don't usually detect it until late in its course.