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A study published in the Journal of the American Medical Association (JAMA) involving nearly 17,000 U.S. smokers confirms that women are twice as likely to develop lung cancer as men.

Paradoxically, the new findings also suggest that women are more likely than men to survive the disease, should it arise.

The results of this international, multicenter study—led by Dr. Claudia Henschke of NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City—could have important lessons for public health efforts aimed at reducing deaths due to smoking.

"These findings highlight the need to educate younger women that they are at higher risk of developing lung cancer, even when they're smoking the same amount as men," says Dr. Henschke, principal investigator of I-ELCAP and chief of Chest Imaging in the Department of Radiology at NewYork-Presbyterian/Weill Cornell, and professor of radiology at Weill Cornell Medical College. "Based on their excess vulnerability to tobacco smoke, women may also need to get screened for lung cancer earlier than men," she adds.

The findings are published in the July 12 issue of the Journal of the American Medical Association (JAMA).

Lung cancer remains the single largest cancer killer of both sexes in the United States, with more than 90,000 men and 73,000 women falling victim to the disease each year. In fact, lung cancer kills more U.S. women annually than the next two leading malignancies (breast and colon cancer) combined.

And yet, until now, gender differences in lung cancer have been poorly understood.

This study follows up on preliminary research involving 2,490 smokers taking part in the Early Lung Cancer Action Project (ELCAP).

"That first series only included people enrolled in our institution in New York City," Dr. Henschke explains.

The new data includes a total of 7,498 female and 9,427 male smokers who underwent CT lung cancer screening at centers across North America. "The results are now more generalizable to the country as a whole," Dr. Henschke notes.

All of the study participants were current or former smokers aged 40 or older who showed no symptoms of lung cancer at the time of screening. Lung cancer was diagnosed in 156 of the 7,498 female participants (2 percent) and 113 of the 9,427 men in the study (1.2 percent). After adjusting for differences of age and smoking history, women were found to have almost twice the risk of lung cancer (odds ratio of 1.9).

"That means that female smokers were nearly twice as likely to develop lung cancer compared to men of the same age and smoking history," Dr. Henschke said.

But there was another intriguing finding: Women who developed lung cancer were also 52 percent less likely to die from the disease than men (hazard ratio of 0.48), the researchers found.

That statistic held even after adjusting for factors such as smoking history, disease stage at diagnosis, tumor type and interventions such as surgery.

"This clears up some of the long-standing confusion surrounding gender and lung cancer," Dr. Henschke says. "Yes, given the same exposure, women are less likely to die from lung cancer than men, but they also have double the risk of getting the disease."

"We're not really sure why that might be," Dr. Henschke adds. "Is the women's cancer just less aggressive? Or is it more curable? We just don't know, but it's certainly an area that deserves more research," she says.

In the meantime, preventive efforts aimed at young women may be key to lowering lung cancer incidence, she says.

"We have to get the word out to teen girls, especially, that their long-term risk of developing cancer is higher than that of males with similar smoking histories," she says. "The best way to avoid lung cancer is to never take up smoking in the first place."

Women's heightened susceptibility to lung cancer also supports the need for earlier screening for female smokers, Dr. Henschke adds.

"Based on our evidence, we believe that the screening threshold for women of a given age should be some 50 pack-years lower than that of men of the same age," she says.

Screening can and does save lives, Dr. Henschke adds.

"Whatever your gender, early detection remains our very best weapon for beating this terrible disease," she concludes.

Contributing authors include Dr. Nasser Altorki, Dr. Ali Farooqi, Dr. Daniel Libby, Dr. Dorothy I. McCauley, Dr. Mark Pasmantier, Dr. Anthony P. Reeves, Dr. James P. Smith, Dr. Madeline Vazquez, Dr. David F. Yankelevitz, Rowena Yip, Kimberly Agnello, Arin Kramer and Jennifer Hess—all of NewYork-Presbyterian/Weill Cornell.

The I-ELCAP investigators included experts from 37 other academic medical centers worldwide.

Drs. Henschke and Yankelevitz are co-inventors on a patent and other pending patents owned by Cornell Research Foundation (CRF), which are non-exclusively licensed to General Electric and related to technology involving computer-aided diagnostic methods, including measurement of nodules.