Lung Cancer Risk for Never-Smokers Higher for Women than Men

STANFORD, Calif., Feb. 9 -- For reasons that are speculative at best, women who never smoked are more likely to get lung cancer than are men who never took up the habit, according to researchers here.

Data from several large cohorts of volunteers shows that the rate of lung cancer among women who never smoked ranges from 14.4 to 20.8 cases per 100,000 people, found Heather Wakelee, M.D., of Stanford.

In contrast, the rate among male never-smokers was 4.8 to 13.7 cases per 100,000 people, Dr. Wakelee and colleagues reported in the Feb. 10 issue of the Journal of Clinical Oncology.

If the figures from the various study groups are representative of the U.S. population as a whole, the researchers said, it's likely that about 8% of men and 20% of women with lung cancer never smoked.

The findings are important as a first step in understanding the epidemiology of lung cancer among people who don't smoke, the researchers said.

"We can actually put numbers on it now," Dr. Wakelee said. "Before this, we could only estimate based on our own census."

The research harkens back to the widely-publicized case of Dana Reeve, widow of the actor Christopher Reeve, who was a lifelong non-smoker, but died of lung cancer in March 2006.

Dr. Wakelee and colleagues used six large longitudinal cohorts, five in the U.S. and one in Sweden, to extract data on lung cancer occurrence rates among men and women ages 40 to 79.

In the studies, which included more than one million people, the rates per 100,000 were:

• 15.2 for women in the Nurses' Health Study.
• 11.2 for men in the Health Professionals Follow-Up Study.
• 20.8 among women in the California Teachers Study.
• 13.7 for men and 20.7 for women in the Multiethnic Cohort Study.
• 4.8 for men and 14.4 for women in the Swedish Lung Cancer Register (Uppsala/Orebro region).
• 12.7 for men and 19.3 for women in the First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study.

By comparison, the researchers said, age-adjusted occurrence rates among smokers were between 12 and 30 times higher, depending on the cohort.

The Swedish rates were lower, which is consistent with a lower lung cancer rate in general, the researchers said, but the rates among the U.S. studies were comparable.

The Stanford study was unable to say whether the occurrence rate of lung cancer is rising among non-smokers, although the researchers pointed out that the rates were slightly higher in later studies, such as the California Teachers Study, compared with the earlier cohorts, such as the Nurses' Health Study.

But the differences were not statistically significant, they said.

In the absence of the most important risk factor - cigarette smoking - it's not clear why people develop lung cancer, said study co-author Ellen Chang, Sc.D., an epidemiologist at the Northern California Cancer Center here.

She said second-hand smoke might explain part of the difference. Because more men smoke, women may be more likely to be exposed to secondhand smoke, even when they are classified as never-smokers.

Other possibilities include occupational exposures, domestic radon, indoor pollution, genetic factors, and dietary factors, the researchers said.

Clinically, the etiology of lung cancer is important for several reasons, Dr Wakelee and colleagues noted:

• Patients who never smoked are significantly more likely to respond well to drugs that target the epidermal growth factor receptor, such as Iressa (gefitinib) and Tarceva (erlotinib).
• Regardless of therapy, never-smokers with non-small-cell lung cancer have a modest survival benefit compared with smokers.
• Never-smokers are more likely to present with an adenocarcinoma, rather than squamous cell or other histological type of disease.