Lung cancer rates higher among female nonsmokers than thought

Not all lung cancer is due to a lifetime of smoking cigarettes. Sometimes the diagnosis is a mystery, and the stigma surrounding the disease makes it hard for patients to talk about. Now, researchers at the Stanford University School of Medicine and the Northern California Cancer Center have taken the first steps toward analyzing why people who never smoked get lung cancer.

Their data, to be published in the Feb. 10 issue of the Journal of Clinical Oncology, shows that never-smokers get lung cancer more often than thought, with women even more at risk than men.

“People tend to banter about this number of 10 to 15 percent of lung cancer cases being in people who have never smoked,” explained lead author Heather Wakelee, MD, assistant professor of medicine at Stanford. “But when you actually try to find the hard data to show that, it’s very limited.”

The team of researchers used multiple collections of data from both the United States and Sweden that, in total, tracked the incidence of lung cancer in more than 1 million people from the ages of 40 to 79. They calculated the lung cancer incidence rates in terms of new cases per person-year, representing every year that someone was included in the study.

They found that for women, the lung cancer incidence rate in never-smokers ranged from 14.4 to 20.8 cases per 100,000 person-years. In men, it ranged from 4.8 to 13.7 incidents. For current smokers, the rates were about 10 to 30 times higher. To put these numbers in perspective, Wakelee pointed out that the rates for cervical and thyroid cancer in women of the same age range are comparable, at 15.4 and 17.3 cases per 100,000 person-years, respectively.

If these statistics are representative of the overall population of the United States, the authors infer that around 8 percent of lung cancer cases in males and close to 20 percent of cases in females are among never-smokers. “We can actually put numbers on it now,” said Wakelee. “Before this, we could only estimate based on our own census.”

Co-author Ellen Chang, ScD, an epidemiologist at the Northern California Cancer Center and a member of the Stanford Comprehensive Cancer Center, cautioned that it is difficult to study many of the factors that could affect these statistics. For example, secondhand smoke exposure could explain part of the gender difference that the team found. Because more men smoke than women, explained Chang, women may be more likely to be exposed to secondhand smoke, even when they are classified as never-smokers.

“We know that secondhand smoke does increase the risk of lung cancer,” she said, “so it’s likely that a lot of these cases we observe are attributable to that.”

Wakelee added that a number of environment pollutants and occupational exposures, including asbestos, chromium, arsenic and radon, are thought to cause lung cancer in never-smokers, but these links have not been unquestionably proven. Eventually showing which factors increase the chances of never-smokers developing lung cancer will allow doctors to understand, at a molecular level, how the cancer works. And this, Wakelee hopes, will lead to new treatment options.

Already, scientists know that some therapies work better in lung cancer patients who never smoked because the histology of their tumors is different.

Clinical observations have suggested an upward trend in non-smoking-associated lung cancer rates, and the Stanford researchers hope their data can eventually be used to test this. They see their current work as a baseline, and want future studies of the same type to allow them to extrapolate a trend.

The team also hopes that by studying lung cancer in never-smokers, they can alleviate some of the stereotypes associated with the disease.

“I have a lot of patients who have never smoked,” said Wakelee. “And because of the stigma, people are embarrassed to speak out about their disease. They feel like as soon as they say they have lung cancer, everyone judges them.” She added that the stigma affects not only patients’ lives, but funding and support for researchers.

More than 180,000 Americans are diagnosed with lung cancer every year, and it kills more patients than breast, colon and prostate cancers combined. Wakelee looks forward to the day that the symbol for lung cancer support, a clear ribbon, is easily recognized. Already, she said, celebrity cases like Dana Reeve have brought non-smoking-related lung cancer to the public’s attention.

“Non-smoking-associated lung cancer is an increasingly important issue,” added Chang, “even if only because the population of never-smokers is growing.”

From Stanford University Medical Center

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